Israel Journal of Chemistry最新文献

{"title":"Richard A. Lerner: Memories and Reflections","authors":"Paul Schimmel","doi":"10.1002/ijch.202300149","DOIUrl":"https://doi.org/10.1002/ijch.202300149","url":null,"abstract":"<p>Richard Lerner was a singularity. During his tenure, Scripps Research was transformed into a biomedical powerhouse. He rapidly built remarkable strength in chemical and structural biology, immunology, cell and molecular biology, and molecular medicine. Not to stop there, he also instituted a new graduate program that consistently ranked in the top ten in the US. At the same time, he was a prolific author of scientific papers, which poured out of his own laboratory with colleagues at Scripps Research and collaborators throughout the world. These and many other aspects of his brilliant career and contributions are well documented and discussed elsewhere.</p><p>Here I chose to avoid redundancy and focus instead on a few of the personal encounters, which give some sense of Richard's character and spirit. An essential part of Richard's success was his wife Nicola (Nicky), herself an MD, who worked tirelessly to enable him to achieve what he did. Early on, my wife Cleo and Nicky became close friends. This relationship facilitated social occasions, where we would be with the Lerner's at a dinner or event, sometimes at our home or at theirs, but also with guests at various restaurants in La Jolla. As a result, my understanding of Richard was broadened beyond that received from the many discussions and meetings at Scripps Research. This understanding was helpful during those times when we faced serious challenges and he, like all of us when under stress, needed support.</p><p>In what is written below, I have used plain language to relate some of my memories and reflections. Richard was a friend and colleague and taught me much, especially the power of a vision, of belief in that vision and of the will to make the effort to bring it to pass.</p>","PeriodicalId":14686,"journal":{"name":"Israel Journal of Chemistry","volume":"63 10-11","pages":""},"PeriodicalIF":3.2,"publicationDate":"2023-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ijch.202300149","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138454692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Memory of Prof. Richard A. Lerner","authors":"","doi":"10.1002/ijch.202300160","DOIUrl":"https://doi.org/10.1002/ijch.202300160","url":null,"abstract":"&lt;p&gt;Dear Reader,&lt;/p&gt;&lt;p&gt;This Special Issue has been put together to honor the life and work of Prof. Richard A. Lerner (August 28, 1938–December 2, 2021), whose visionary presidential leadership and guidance for over a quarter century (1987–2012) catapulted The Scripps Research Institute (La Jolla, California and Jupiter, Florida) into a powerhouse at the interface of chemistry, biology, and medicine. Following is a colorful assortment of twenty contributions that collectively paint a picture of a man who intuitively and ingeniously blended organic chemistry and immunology to arrive at new molecular compositions and concepts that have defined contemporary small and large-molecule drug discovery.&lt;/p&gt;&lt;p&gt;Prof. Lerner's mix of creativity, fearlessness, and unboundedness conceived and conceptualized inventions like catalytic antibodies, antibody libraries, and DNA-encoded small molecule libraries. Several articles in this Special Issue pay tribute to these transformative discoveries, depicted in the cover image. Other articles add additional facets to the theme of bioinspired chemistry. Sprinkled in are numerous anecdotes of Prof. Lerner's rebellious and humorous nature that made him, as his friend and presidential successor at Scripps Research, Prof. Peter G. Schultz, notes, “one of a kind […] who defied boundaries and lived life to its fullest.”&lt;/p&gt;&lt;p&gt;Above all, Prof. Lerner was an enabler of ideas who recruited, protected and connected brilliant minds at every academic level at The Scripps Research Institute (now Scripps Research). He cherished their discoveries at least as much as his own, corroborated by one of his mentees, Prof. Benjamin F. Cravatt, who writes in his contribution, “I have never met someone so accomplished who took their greatest joy in the accomplishments of others.” Prof. Lerner's infectious energy and enthusiasm catalyzed the careers of graduate students, postdocs, and faculty on both the Pacific and Atlantic campuses of Scripps Research, as well as beyond the United States, as reflected here by contributions from Israel, Korea, Russia, Sweden, Switzerland, and the United Kingdom. Many of us have come together for this Special Issue as a tribute to the unconventional explorer, builder, and leader who transformed and empowered our thinking and doing. We are fortunate to have crossed paths with him.&lt;/p&gt;&lt;p&gt;Since the Israel Journal of Chemistry is the official Journal of the Israel Chemical Society (ICS), we welcome the recently established ICS-Lerner Prize and Lectureship that commemorates the legacy of Prof. Richard A. Lerner. This international Prize has become possible based on a $100 K endowment fund, which secures the Prize perpetually. All ICS members thank and congratulate the donors, Professors Phil S. Baran, Benjamin F. Cravatt, Jeffery W. Kelly, Chi-Huey Wong, Jin-Quan Yu, and Dr. Phillip Frost. The Organic Chemistry Section of the ICS will handle the ICS-Lerner Prize annually, planning to announce the first winner in Jan","PeriodicalId":14686,"journal":{"name":"Israel Journal of Chemistry","volume":"63 10-11","pages":""},"PeriodicalIF":3.2,"publicationDate":"2023-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ijch.202300160","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138454739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Richard Lerner and the Birth of Antibody Libraries","authors":"Dennis R. Burton","doi":"10.1002/ijch.202300151","DOIUrl":"https://doi.org/10.1002/ijch.202300151","url":null,"abstract":"<p>Richard Lerner had many achievements in his outstanding career. He will perhaps be remembered most for taking the helm of Scripps Research, following the founding by and tenure of Frank Dixon, and building one of the most successful biomedical research institutes in the world. Two Nobel prizes at Scripps in the past two years and one of them a second Nobel speaks for itself. But I want to cover what many consider Richard's finest scientific achievement- the development of a whole new approach to making antibodies that has been revolutionary to many aspects of basic science and medicine. I was very fortunate to be a part of that development and I give an account here and my memories of Richard during that time.</p>","PeriodicalId":14686,"journal":{"name":"Israel Journal of Chemistry","volume":"63 10-11","pages":""},"PeriodicalIF":3.2,"publicationDate":"2023-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ijch.202300151","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138454691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Richard A. Lerner – Little Known Facets of an Outstanding Man","authors":"Ehud Keinan","doi":"10.1002/ijch.202300140","DOIUrl":"https://doi.org/10.1002/ijch.202300140","url":null,"abstract":"<p>Richard was mainly known as a gifted scientist, a charismatic leader, and an original and creative President. And he was my good friend and a role model for over three decades. The term impossible was not part of his vocabulary. I′ve learned from him that there is no limit to imagination and creativity, no limit to the number of assignments one can fulfill, and no limit to the magnitude of a dream one can turn into reality. Richard was blessed with the unique talent to quickly decipher the essence of people‘s thoughts and discover the hidden parts of their personalities, which allowed him to focus on what he defined as the most valuable issues and productive discussions. My experience with him included the joy of scientific discovery, the silent mode of human communication, the power of commitment and dedication, and the wildest sense of humor. Now, nearly two years after his departure, I feel free and obliged to share unknown stories and anecdotes that illuminate various facets of his personality.</p>","PeriodicalId":14686,"journal":{"name":"Israel Journal of Chemistry","volume":"63 10-11","pages":""},"PeriodicalIF":3.2,"publicationDate":"2023-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138454689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Richard Lerner (1938–2021)","authors":"Dr. Peter G. Schultz","doi":"10.1002/ijch.202300150","DOIUrl":"https://doi.org/10.1002/ijch.202300150","url":null,"abstract":"<p>\u0000 \u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":14686,"journal":{"name":"Israel Journal of Chemistry","volume":"63 10-11","pages":""},"PeriodicalIF":3.2,"publicationDate":"2023-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138454690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"STEM Structural Investigation of RE‐Au‐Si 1/1 Approximants","authors":"Wilfried Bajoun Mbajoun, Vinko Sršan, Yu‐Chin. Huang, Girma Hailu Gebresenbut, Cesar Pay Gómez, Sylvie Migot‐Choux, Jaafar Ghanbaja, Sašo Šturm, Vincent Fournée, Julian Ledieu","doi":"10.1002/ijch.202300117","DOIUrl":"https://doi.org/10.1002/ijch.202300117","url":null,"abstract":"Abstract RE‐Au‐Si (RE=Ho, Tb) systems are 1/1 Tsai‐type quasicrystalline approximants with a cluster center decoration that can vary from a disordered tetrahedron to a rare‐earth atom. The local atomic structure of three different samples was observed by scanning transmission electron microscopy and interpreted in the light of high‐angle annular dark field simulated scanning transmission electron microscopy images. It is found that the combination of these two methods allows to identify differences in the chemical decoration of the cluster centers through quantitative analysis of line profiles.","PeriodicalId":14686,"journal":{"name":"Israel Journal of Chemistry","volume":"11 5","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134901655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent Advances in Electrochemical Reductive Transformation of C−C and C−O Multiple Bonds","authors":"Atreyee Halder,&nbsp;Kingshuk Mahanty,&nbsp;Debabrata Maiti,&nbsp;Dr. Suman De Sarkar","doi":"10.1002/ijch.202300102","DOIUrl":"10.1002/ijch.202300102","url":null,"abstract":"<p>In recent decades, electro-organic synthesis is indubitably emerging as a cornerstone of modern organic chemistry. Electrochemical organic transformations especially reduction reactions have made massive advancements in the last few years because of their sustainable and environ-friendly nature. Electro-reductive protocols can be used as a promising substitute for conventional reductants by expelling the requirement of the stoichiometric amount of metal reductants. The major challenges for these electro-reductive reactions are primarily the use of a sacrificial electrode and divided cells. These limitations can be resolved through smart reaction planning by employing cheap sacrificial reagents or paired electrolysis without compromising the sustainable viewpoint. Considering the rapid enhancement in this field, imparting an intangible understanding of this evolving area is essential and substantial. In this review, we portrayed the electrochemical reductive transformations of C−C and C−O bonds after 2015 along with detailed mechanistic insights.</p>","PeriodicalId":14686,"journal":{"name":"Israel Journal of Chemistry","volume":"64 1-2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2023-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135341166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacologic Targeting of PDIA1 Inhibits NLRP3 Inflammasome Assembly and Activation","authors":"Jessica D. Rosarda, Caroline R. Stanton, Emily B. Chen, Michael J. Bollong, R. Luke Wiseman","doi":"10.1002/ijch.202300125","DOIUrl":"https://doi.org/10.1002/ijch.202300125","url":null,"abstract":"Abstract The NLRP3 inflammasome is a cytosolic protein complex that regulates innate immune signaling in response to diverse pathogenic insults through the proteolytic processing and secretion of pro‐inflammatory cytokines such as IL‐1β. Hyperactivation of NLRP3 inflammasome signaling is implicated in the onset and pathogenesis of numerous diseases, motivating the discovery of new strategies to suppress NLRP3 inflammasome activity. We sought to define the potential for the proteostasis regulator AA147 to inhibit the assembly and activation of the NLRP3 inflammasome. AA147 is a pro‐drug that is metabolically converted to a reactive metabolite at the endoplasmic reticulum (ER) membrane to covalently modify ER‐localized proteins such as protein disulfide isomerases (PDIs). We show that AA147 inhibits NLRP3 inflammasome activity in monocytes and monocyte‐derived macrophages through a mechanism involving impaired assembly of the active inflammasome complex. This inhibition is mediated through AA147‐dependent covalent modification of PDIA1. Genetic depletion or treatment with other highly selective PDIA1 inhibitors similarly blocks NLRP3 inflammasome assembly and activation. Our results identify PDIA1 as a potential therapeutic target to mitigate NLRP3 inflammasome‐mediated pro‐inflammatory signaling implicated in etiologically diverse diseases.","PeriodicalId":14686,"journal":{"name":"Israel Journal of Chemistry","volume":"14 S1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135341332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of the Proteasome in Limiting Cellular Stress Associated with Protein Accumulation","authors":"Kate A. Kragness, Darci J. Trader","doi":"10.1002/ijch.202300120","DOIUrl":"https://doi.org/10.1002/ijch.202300120","url":null,"abstract":"Abstract The proteasome is comprised of multiple subunits that catalyze the degradation of proteins to maintain cellular homeostasis. The proteasome targets protein substrates by two different pathways. The ubiquitin‐dependent pathway requires proteins to be labeled with a ubiquitin tag to signal for degradation by the 26S isoform of the proteasome. Protein degradation through this pathway declines during age progression. The ubiquitin‐independent pathway utilizes the 20S proteasome isoform. It can degrade misfolded and intrinsically disordered proteins to decrease cellular stress. Age‐related protein accumulation and aggregation can occur due to the decreased activity and expression of the proteasome. Protein accumulation causes increased cellular stress which can contribute to disease progression. Increasing proteasome activity could serve as a solution to eliminating and preventing protein accumulation. Studies have shown the value of the proteasome as a therapeutic entity to mitigate cellular stress. This perspective explores the link between proteasome activity and cellular stress caused by age‐related misfolded protein accumulation.","PeriodicalId":14686,"journal":{"name":"Israel Journal of Chemistry","volume":"48 2","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135480424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding and Overcoming Biochemical Diversity in AL Amyloidosis","authors":"Gareth J. Morgan","doi":"10.1002/ijch.202300128","DOIUrl":"https://doi.org/10.1002/ijch.202300128","url":null,"abstract":"Abstract Amyloid fibril deposition causes progressive tissue damage and organ failure in the systemic amyloid diseases, and therapies that suppress aggregation lead to clinical benefit. Small molecules that prevent aggregation by binding to precursor proteins are effective for amyloid transthyretin (ATTR) amyloidosis. However, in amyloid light chain (AL) amyloidosis, fibrils are formed by antibody light chains and every patient has a unique protein sequence that aggregates. The highly diverse sequences of these light chains appear to determine whether an individual is at risk of amyloidosis, the distribution of amyloid deposits and the progression of disease. Light chains are therefore challenging drug targets. This review explores the parallels between AL amyloidosis and ATTR amyloidosis to describe the discovery of small molecules that can stabilize light chains. These molecules have potential as therapies for AL amyloidosis, highlighting potential opportunities for drug discovery in other diseases of protein misfolding.","PeriodicalId":14686,"journal":{"name":"Israel Journal of Chemistry","volume":"15 3","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135679326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}