In vivo degradation forms, anti-degradation strategies, and clinical applications of therapeutic peptides in non-infectious chronic diseases

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dc.contributor.authorTasdemiroglu, Yagmuren
dc.contributor.authorGourdie, Robert G.en
dc.contributor.authorHe, Jia-Qiangen
dc.date.accessioned2023-01-17T17:54:48Zen
dc.date.available2023-01-17T17:54:48Zen
dc.date.issued2022-10-15en
dc.date.updated2023-01-16T15:25:17Zen
dc.description.abstractCurrent medicinal treatments for diseases comprise largely of two categories: small molecular (chemical) (e.g., aspirin) and larger molecular (peptides/proteins, e.g., insulin) drugs. Whilst both types of therapeutics can effectively treat different diseases, ranging from well-understood (in view of pathogenesis and treatment) examples (e.g., flu), to less-understood chronic diseases (e.g., diabetes), classical small molecule drugs often possess significant side-effects (a major cause of drug withdrawal from market) due to their low- or non-specific targeting. By contrast, therapeutic peptides, which comprise short sequences from naturally occurring peptides/proteins, commonly demonstrate high target specificity, well-characterized modes-of-action, and low or non-toxicity in vivo. Unfortunately, due to their small size, linear permutation, and lack of tertiary structure, peptidic drugs are easily subject to rapid degradation or loss in vivo through chemical and physical routines, thus resulting in a short half-life and reduced therapeutic efficacy, a major drawback that can reduce therapeutic efficiency. However, recent studies demonstrate that the short half-life of peptidic drugs can be significantly extended by various means, including use of enantiomeric or non-natural amino acids (AAs) (e.g., L-AAs replacement with D-AAs), chemical conjugation [e.g., with polyethylene glycol], and encapsulation (e.g., in exosomes). In this context, we provide an overview of the major in vivo degradation forms of small therapeutic peptides in the plasma and anti-degradation strategies. We also update on the progress of small peptide therapeutics that are either currently in clinical trials or are being successfully used in clinical therapies for patients with non-infectious diseases, such as diabetes, multiple sclerosis, and cancer.en
dc.description.versionAccepted versionen
dc.format.mimetypeapplication/pdfen
dc.identifier175192 (Article number)en
dc.identifier.doihttps://doi.org/10.1016/j.ejphar.2022.175192en
dc.identifier.eissn1879-0712en
dc.identifier.issn0014-2999en
dc.identifier.orcidGourdie, Robert [0000-0001-6021-0796]en
dc.identifier.orcidHe, Jia-Qiang [0000-0002-0640-5960]en
dc.identifier.otherS0014-2999(22)00453-8 (PII)en
dc.identifier.pmid35981605en
dc.identifier.urihttp://hdl.handle.net/10919/113202en
dc.identifier.volume932en
dc.language.isoenen
dc.publisherElsevieren
dc.relation.urihttps://www.ncbi.nlm.nih.gov/pubmed/35981605en
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectAnti-degradation strategiesen
dc.subjectClinical applicationsen
dc.subjectIn vivo degradation formsen
dc.subjectTherapeutic peptideen
dc.subjectRare Diseasesen
dc.subjectDiabetesen
dc.subjectOrphan Drugen
dc.subject5.1 Pharmaceuticalsen
dc.subject5 Development of treatments and therapeutic interventionsen
dc.subjectMetabolic and endocrineen
dc.subject3 Good Health and Well Beingen
dc.subject.meshHumansen
dc.subject.meshDiabetes Mellitusen
dc.subject.meshPolyethylene Glycolsen
dc.subject.meshAspirinen
dc.subject.meshAmino Acidsen
dc.subject.meshPeptidesen
dc.subject.meshProteinsen
dc.subject.meshInsulinsen
dc.subject.meshNoncommunicable Diseasesen
dc.titleIn vivo degradation forms, anti-degradation strategies, and clinical applications of therapeutic peptides in non-infectious chronic diseasesen
dc.title.serialEuropean Journal of Pharmacologyen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherJournalen
dcterms.dateAccepted2022-08-05en
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/Veterinary Medicineen
pubs.organisational-group/Virginia Tech/Veterinary Medicine/Biomedical Sciences and Pathobiologyen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Veterinary Medicine/CVM T&R Facultyen
pubs.organisational-group/Virginia Tech/VT Carilion School of Medicineen
pubs.organisational-group/Virginia Tech/VT Carilion School of Medicine/Internal Medicineen
pubs.organisational-group/Virginia Tech/VT Carilion School of Medicine/Emergency Medicineen
pubs.organisational-group/Virginia Tech/VT Carilion School of Medicine/Emergency Medicine/Emergency Medicineen
pubs.organisational-group/Virginia Tech/VT Carilion School of Medicine/Emergency Medicine/Emergency Medicine/Secondary Appointment-Emergency Medicineen
pubs.organisational-group/Virginia Tech/VT Carilion School of Medicine/Internal Medicine/Internal Med-Subgroupen
pubs.organisational-group/Virginia Tech/University Research Institutesen
pubs.organisational-group/Virginia Tech/University Research Institutes/Fralin Biomedical Research Institute at VTCen

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