ACS Bio & Med Chem Au最新文献

{"title":"Modeling the Effect of Cooperativity in Ternary Complex Formation and Targeted Protein Degradation Mediated by Heterobifunctional Degraders","authors":"Daniel Park,&nbsp;Jesus Izaguirre,&nbsp;Rory Coffey and Huafeng Xu*,&nbsp;","doi":"10.1021/acsbiomedchemau.2c00037","DOIUrl":"10.1021/acsbiomedchemau.2c00037","url":null,"abstract":"<p >Chemically induced proximity between certain endogenous enzymes and a protein of interest (POI) inside cells may cause post-translational modifications to the POI with biological consequences and potential therapeutic effects. Heterobifunctional (HBF) molecules that bind with one functional part to a target POI and with the other to an E3 ligase induce the formation of a target-HBF-E3 ternary complex, which can lead to ubiquitination and proteasomal degradation of the POI. Targeted protein degradation (TPD) by HBFs offers a promising approach to modulate disease-associated proteins, especially those that are intractable using other therapeutic approaches, such as enzymatic inhibition. The three-way interactions among the HBF, the target POI, and the ligase─including the protein–protein interaction between the POI and the ligase─contribute to the stability of the ternary complex, manifested as positive or negative binding cooperativity in its formation. How such cooperativity affects HBF-mediated degradation is an open question. In this work, we develop a pharmacodynamic model that describes the kinetics of the key reactions in the TPD process, and we use this model to investigate the role of cooperativity in the ternary complex formation and in the target POI degradation. Our model establishes the quantitative connection between the ternary complex stability and the degradation efficiency through the former’s effect on the rate of catalytic turnover. We also develop a statistical inference model for determining cooperativity in intracellular ternary complex formation from cellular assay data and demonstrate it by quantifying the change in cooperativity due to site-directed mutagenesis at the POI-ligase interface of the SMARCA2-ACBI1-VHL ternary complex. Our pharmacodynamic model provides a quantitative framework to dissect the complex HBF-mediated TPD process and may inform the rational design of effective HBF degraders.</p>","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"3 1","pages":"74–86"},"PeriodicalIF":0.0,"publicationDate":"2022-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/63/44/bg2c00037.PMC10125322.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9355993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling the Chemistry of meso-Cl Tricarbocyanine Dyes in Conjugation Reactions for the Creation of Peptide Bonds","authors":"Rüdiger M. Exner,&nbsp;Fernando Cortezon-Tamarit,&nbsp;Haobo Ge,&nbsp;Charareh Pourzand and Sofia I. Pascu*,&nbsp;","doi":"10.1021/acsbiomedchemau.2c00053","DOIUrl":"https://doi.org/10.1021/acsbiomedchemau.2c00053","url":null,"abstract":"<p >Tricarbocyanine dyes have become popular tools in life sciences and medicine. Their near-infrared (NIR) fluorescence makes them ideal agents for imaging of thick specimens or <i>in vivo</i> imaging, <i>e.g.</i>, in fluorescence-guided surgery. Among other types of cyanine dyes, <i>meso</i>-Cl tricarbocyanine dyes have received a surge of interest, as it emerged that their high reactivity makes them inherently tumor-targeting. As such, significant research efforts have focused on conjugating these to functional moieties. However, the syntheses generally suffer from low yields. Hereby, we report on the reaction of <i>meso</i>-Cl dyes with a small selection of coupling reagents to give the corresponding keto-polymethines, potentially explaining low yields and the prevalence of monofunctionalized cyanine conjugates in the current state of the art of functional near-infrared dyes. We present the synthesis and isolation of the first keto-polymethine-based conjugate and present preliminary investigation in the prostate cancer cell lines PC3 and DU145 by confocal microscopy and discuss changes to optical properties in biological media.</p>","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"2 6","pages":"642–654"},"PeriodicalIF":0.0,"publicationDate":"2022-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acsbiomedchemau.2c00053","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72202262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-Specific Silica Nanoparticle Protein Corona Compositions Exposed to Male and Female BALB/c Mice Plasmas","authors":"Ali Akbar Ashkarran,&nbsp;Hassan Gharibi,&nbsp;Jason W. Grunberger,&nbsp;Amir Ata Saei*,&nbsp;Nitish Khurana,&nbsp;Raziye Mohammadpour,&nbsp;Hamidreza Ghandehari and Morteza Mahmoudi*,&nbsp;","doi":"10.1021/acsbiomedchemau.2c00040","DOIUrl":"10.1021/acsbiomedchemau.2c00040","url":null,"abstract":"<p >As various nanoparticles (NPs) are increasingly being used in nanomedicine products for more effective and less toxic therapy and diagnosis of diseases, there is a growing need to understand their biological fate in different sexes. Herein, we report a proof-of-concept result of sex-specific protein corona compositions on the surface of silica NPs as a function of their size and porosity upon incubation with plasma proteins of female and male BALB/c mice. Our results demonstrate substantial differences between male and female protein corona profiles on the surface of silica nanoparticles. By comparing protein abundances between male and female protein coronas of mesoporous silica nanoparticles and Stöber silica nanoparticles of ∼100, 50, and 100 nm in diameter, respectively, we detected 17, 4, and 4 distinct proteins, respectively, that were found at significantly different concentrations for these constructs. These initial findings demonstrate that animal sex can influence protein corona formation on silica NPs as a function of the physicochemical properties. A more thorough consideration of the role of plasma sex would enable nanomedicine community to design and develop safer and more efficient diagnostic and therapeutic nanomedicine products for both sexes.</p>","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"3 1","pages":"62–73"},"PeriodicalIF":0.0,"publicationDate":"2022-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9f/61/bg2c00040.PMC9936498.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10470842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Fluorescence-Based Assay to Probe Inhibitory Effect of Fructose Mimics on GLUT5 Transport in Breast Cancer Cells","authors":"Natasha Rana,&nbsp;Marwa A. Aziz,&nbsp;Rabah A. T. Serya,&nbsp;Deena S. Lasheen,&nbsp;Nermin Samir,&nbsp;Frank Wuest,&nbsp;Khaled A. M. Abouzid and F. G. West*,&nbsp;","doi":"10.1021/acsbiomedchemau.2c00056","DOIUrl":"10.1021/acsbiomedchemau.2c00056","url":null,"abstract":"<p >Rapid cell division and reprogramming of energy metabolism are two crucial hallmarks of cancer cells. In humans, hexose trafficking into cancer cells is mainly mediated through a family of glucose transporters (GLUTs), which are facilitative transmembrane hexose transporter proteins. In several breast cancers, fructose can functionally substitute glucose as an alternative energy supply supporting rapid proliferation. GLUT5, the principal fructose transporter, is overexpressed in human breast cancer cells, providing valuable targets for breast cancer detection as well as selective targeting of anticancer drugs using structurally modified fructose mimics. Herein, a novel fluorescence assay was designed aiming to screen a series of C-3 modified 2,5-anhydromannitol (2,5-AM) compounds as <span>d</span>-fructose analogues to explore GLUT5 binding site requirements. The synthesized probes were evaluated for their ability to inhibit the uptake of the fluorescently labeled <span>d</span>-fructose derivative 6-NBDF into EMT6 murine breast cancer cells. A few of the compounds screened demonstrated highly potent single-digit micromolar inhibition of 6-NBDF cellular uptake, which was substantially more potent than the natural substrate <span>d</span>-fructose, at a level of 100-fold or more. The results of this assay are consistent with those obtained from a previous study conducted for some selected compounds against ¹⁸F-labeled <span>d</span>-fructose-based probe 6-[¹⁸F]FDF, indicating the reproducibility of the current non-radiolabeled assay. These highly potent compounds assessed against 6-NBDF open avenues for the development of more potent probes targeting GLUT5-expressing cancerous cells.</p>","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"3 1","pages":"51–61"},"PeriodicalIF":0.0,"publicationDate":"2022-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d1/22/bg2c00056.PMC10125380.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9725803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Forodesine and Riboprine Exhibit Strong Anti-SARS-CoV-2 Repurposing Potential: In Silico and In Vitro Studies","authors":"Amgad M. Rabie*,&nbsp; and ,&nbsp;Mohnad Abdalla*,&nbsp;","doi":"10.1021/acsbiomedchemau.2c00039","DOIUrl":"https://doi.org/10.1021/acsbiomedchemau.2c00039","url":null,"abstract":"<p >Lately, nucleos(t)ide antivirals topped the scene as top options for the treatment of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Targeting the two broadly conserved SARS-CoV-2 enzymes, RNA-dependent RNA polymerase (RdRp) and 3′-to-5′ exoribonuclease (ExoN), together using only one shot is a very successful new tactic to stop SARS-CoV-2 multiplication irrespective of the SARS-CoV-2 variant type. Herein, the current studies investigated most nucleoside analogue (NA) libraries, searching for the ideal drug candidates expectedly able to act through this double tactic. Gradual computational filtration gave rise to six different promising NAs along with their corresponding triphosphate (TP) nucleotides. The subsequent biological assessment proved for the first time that, among the six NAs, riboprine and forodesine are able to hyperpotently inhibit the replication of the Omicron strain of SARS-CoV-2 with extremely low <i>in vitro</i> anti-RdRp, anti-ExoN, and anti-SARS-CoV-2 EC₅₀ values of about 0.18, 0.28, and 0.40 μM for riboprine and about 0.20, 0.31, and 0.65 μM for forodesine, respectively, surpassing remdesivir and molnupiravir. The significant probability that both compounds may also act as prodrugs for their final TP nucleotides <i>in vivo</i> pushed us to examine the same activities for forodesine-TP and riboprine-TP. Both nucleotides similarly displayed very promising results, respectively, which are much better than those for the two reference TP nucleotides, GS-443902 and β-<span>d</span>-<i>N</i>⁴-hydroxycytidine 5′-TP (NHC-TP). The prior <i>in silico</i> data supported these biochemical findings, suggesting that riboprine and forodesine molecules and their expected active TP metabolites strongly hit the key catalytic pockets of the SARS-CoV-2 RdRp’s and ExoN’s main active sites. In brief, the current important results of this comprehensive study revealed the interesting repurposing potentials of, mainly, the two bioactive nucleosides forodesine and riboprine and their TP nucleotides to effectively shut down the polymerase/exoribonuclease-RNA nucleotide interactions of SARS-CoV-2 and consequently treat COVID-19 infections.</p>","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"2 6","pages":"565–585"},"PeriodicalIF":0.0,"publicationDate":"2022-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acsbiomedchemau.2c00039","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72200956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual-Reporter System for Real-Time Monitoring of SARS-CoV-2 Main Protease Activity in Live Cells Enables Identification of an Allosteric Inhibition Path","authors":"Yaron Bram,&nbsp;Xiaohua Duan,&nbsp;Benjamin E. Nilsson-Payant,&nbsp;Vasuretha Chandar,&nbsp;Hao Wu,&nbsp;Derek Shore,&nbsp;Alvaro Fajardo,&nbsp;Saloni Sinha,&nbsp;Nora Hassan,&nbsp;Harel Weinstein*,&nbsp;Benjamin R. TenOever*,&nbsp;Shuibing Chen* and Robert E. Schwartz*,&nbsp;","doi":"10.1021/acsbiomedchemau.2c00034","DOIUrl":"10.1021/acsbiomedchemau.2c00034","url":null,"abstract":"<p >The SARS-CoV-2 pandemic is an ongoing threat to global health, and the continuing emergence of contagious variants highlights the urgent need for additional antiviral therapy to attenuate COVID-19 disease. The SARS-CoV-2 main protease (3CL^pro) presents an attractive target for such therapy due to its high sequence conservation and key role in the viral life cycle. In this study, we designed a fluorescent–luminescent cell-based reporter for the detection and quantification of 3CL^pro intracellular activity. Employing this platform, we examined the efficiency of known protease inhibitors against 3CL^pro and further identified potent inhibitors through high-throughput chemical screening. Computational analysis confirmed a direct interaction of the lead compounds with the protease catalytic site and identified a prototype for efficient allosteric inhibition. These developments address a pressing need for a convenient sensor and specific targets for both virus detection and rapid discovery of potential inhibitors.</p>","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"2 6","pages":"627–641"},"PeriodicalIF":0.0,"publicationDate":"2022-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/8d/aa/bg2c00034.PMC9603010.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10440074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activity-Based Sensing for Chemistry-Enabled Biology: Illuminating Principles, Probes, and Prospects for Boronate Reagents for Studying Hydrogen Peroxide","authors":"Marco S. Messina*,&nbsp;Gianluca Quargnali and Christopher J. Chang*,&nbsp;","doi":"10.1021/acsbiomedchemau.2c00052","DOIUrl":"10.1021/acsbiomedchemau.2c00052","url":null,"abstract":"<p >Activity-based sensing (ABS) offers a general approach that exploits chemical reactivity as a method for selective detection and manipulation of biological analytes. Here, we illustrate the value of this chemical platform to enable new biological discovery through a case study in the design and application of ABS reagents for studying hydrogen peroxide (H₂O₂), a major type of reactive oxygen species (ROS) that regulates a diverse array of vital cellular signaling processes to sustain life. Specifically, we summarize advances in the use of activity-based boronate probes for the detection of H₂O₂ featuring high molecular selectivity over other ROS, with an emphasis on tailoring designs in chemical structure to promote new biological principles of redox signaling.</p>","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"2 6","pages":"548–564"},"PeriodicalIF":0.0,"publicationDate":"2022-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9782337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9339528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Practical Synthesis of Antimicrobial Long Linear Polyamine Succinamides","authors":"Abdulaziz H. Alkhzem,&nbsp;Shuxian Li,&nbsp;Toska Wonfor,&nbsp;Timothy J. Woodman,&nbsp;Maisem Laabei and Ian S. Blagbrough*,&nbsp;","doi":"10.1021/acsbiomedchemau.2c00033","DOIUrl":"10.1021/acsbiomedchemau.2c00033","url":null,"abstract":"<p >There are many severe bacterial infections notorious for their ability to become resistant to clinically relevant antibiotics. Indeed, antibiotic resistance is a growing threat to human health, further exacerbated by the lack of new antibiotics. We now describe the practical synthesis of a series of substituted long linear polyamines that produce rapid antibacterial activity against both Gram-positive and Gram-negative bacteria, including meticillin-resistant <i>Staphylococcus aureus</i>. These compounds also reduce biofilm formation in <i>Pseudomonas aeruginosa</i>. The most potent analogues are thermine, spermine, and 1,12-diaminododecane homo- and heterodimeric polyamine succinic acid amides. They are of the order of activity of the aminoglycoside antibiotics kanamycin and tobramycin as positive controls. Their low human cell toxicity is demonstrated in ex vivo hemolytic assays where they did not produce even 5% hemolysis of human erythrocytes. These long, linear polyamines are a new class of broad-spectrum antibacterials active against drug-resistant pathogens.</p>","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"2 6","pages":"607–616"},"PeriodicalIF":0.0,"publicationDate":"2022-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10125363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9711146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"KRAS Inhibitor that Simultaneously Inhibits Nucleotide Exchange Activity and Effector Engagement","authors":"Cynthia V. Pagba,&nbsp;Amit K. Gupta,&nbsp;Ali K. Naji,&nbsp;Dharini van der Hoeven,&nbsp;Kelly Churion,&nbsp;Xiaowen Liang,&nbsp;Jacob Jakubec,&nbsp;Magnus Hook,&nbsp;Yan Zuo,&nbsp;Marisela Martinez de Kraatz,&nbsp;Jeffrey A. Frost and Alemayehu A. Gorfe*,&nbsp;","doi":"10.1021/acsbiomedchemau.2c00045","DOIUrl":"10.1021/acsbiomedchemau.2c00045","url":null,"abstract":"<p >We describe a small molecule ligand <b>ACA-14</b> (2-hydroxy-5-{[(2-phenylcyclopropyl) carbonyl] amino} benzoic acid) as an initial lead for the development of direct inhibitors of KRAS, a notoriously difficult anticancer drug target. We show that the compound binds to KRAS near the switch regions with affinities in the low micromolar range and exerts different effects on KRAS interactions with binding partners. Specifically, <b>ACA-14</b> impedes the interaction of KRAS with its effector Raf and reduces both intrinsic and SOS-mediated nucleotide exchange rates. Likely as a result of these effects, <b>ACA-14</b> inhibits signal transduction through the MAPK pathway in cells expressing mutant KRAS and inhibits the growth of pancreatic and colon cancer cells harboring mutant KRAS. We thus propose compound <b>ACA-14</b> as a useful initial lead for the development of broad-acting inhibitors that target multiple KRAS mutants and simultaneously deplete the fraction of GTP-loaded KRAS while abrogating the effector-binding ability of the already GTP-loaded fraction.</p>","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"2 6","pages":"617–626"},"PeriodicalIF":0.0,"publicationDate":"2022-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/4b/89/bg2c00045.PMC10125367.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9413756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adhesive Virulence Factors of Staphylococcus aureus Resist Digestion by Coagulation Proteases Thrombin and Plasmin","authors":"Fanny Risser,&nbsp;Joanan López-Morales and Michael A. Nash*,&nbsp;","doi":"10.1021/acsbiomedchemau.2c00042","DOIUrl":"https://doi.org/10.1021/acsbiomedchemau.2c00042","url":null,"abstract":"<p ><i>Staphylococcus aureus</i> (<i>S. aureus</i>) is an invasive and life-threatening pathogen that has undergone extensive coevolution with its mammalian hosts. Its molecular adaptations include elaborate mechanisms for immune escape and hijacking of the coagulation and fibrinolytic pathways. These capabilities are enacted by virulence factors including microbial surface components recognizing adhesive matrix molecules (MSCRAMMs) and the plasminogen-activating enzyme staphylokinase (SAK). Despite the ability of <i>S. aureus</i> to modulate coagulation, until now the sensitivity of <i>S. aureus</i> virulence factors to digestion by proteases of the coagulation system was unknown. Here, we used protein engineering, biophysical assays, and mass spectrometry to study the susceptibility of <i>S. aureus</i> MSCRAMMs to proteolytic digestion by human thrombin, plasmin, and plasmin/SAK complexes. We found that MSCRAMMs were highly resistant to proteolysis, and that SAK binding to plasmin enhanced this resistance. We mapped thrombin, plasmin, and plasmin/SAK cleavage sites of nine MSCRAMMs and performed biophysical, bioinformatic, and stability analysis to understand structural and sequence features common to protease-susceptible sites. Overall, our study offers comprehensive digestion patterns of <i>S. aureus</i> MSCRAMMs by thrombin, plasmin, and plasmin/SAK complexes and paves the way for new studies into this resistance and virulence mechanism.</p>","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"2 6","pages":"586–599"},"PeriodicalIF":0.0,"publicationDate":"2022-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acsbiomedchemau.2c00042","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72202053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}