N. Ilieva, E. Lilkova, P. Petkov, Xubiao Peng, Yadi Cheng
{"title":"Biodynamical Implications of Grafting Position Alteration in Engineered Mimics of Parkinson's Inhibitor MCoCP4","authors":"N. Ilieva, E. Lilkova, P. Petkov, Xubiao Peng, Yadi Cheng","doi":"10.7546/crabs.2024.02.06","DOIUrl":null,"url":null,"abstract":"Proteins are currently the fastest-growing class of new therapeutic compounds but smaller proteins and peptides are generally not suitable for use as drugs. Using cyclotides – special knotted proteins stabilized by three pairs of disulphide bonds – as a transport means by grafting onto them as a scaffolding the bioactive peptides can enhance their stability, cellular uptake, and overall efficacy. Experimental methods for creating peptide aptamers are highly time- and resources-consuming. In silico approaches may speed up this process by pre-selecting the drug candidates based on certain biodynamic criteria. In this study, we probe the hypothesis about a relation between the scaffolding conformational stability in conjunction with certain plasticity upon grafting of functionally important domains and the desired biological activity of the modified through the grafting process molecules.","PeriodicalId":104760,"journal":{"name":"Proceedings of the Bulgarian Academy of Sciences","volume":"6 7","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Proceedings of the Bulgarian Academy of Sciences","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.7546/crabs.2024.02.06","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
Proteins are currently the fastest-growing class of new therapeutic compounds but smaller proteins and peptides are generally not suitable for use as drugs. Using cyclotides – special knotted proteins stabilized by three pairs of disulphide bonds – as a transport means by grafting onto them as a scaffolding the bioactive peptides can enhance their stability, cellular uptake, and overall efficacy. Experimental methods for creating peptide aptamers are highly time- and resources-consuming. In silico approaches may speed up this process by pre-selecting the drug candidates based on certain biodynamic criteria. In this study, we probe the hypothesis about a relation between the scaffolding conformational stability in conjunction with certain plasticity upon grafting of functionally important domains and the desired biological activity of the modified through the grafting process molecules.