PepTherDia: database and structural composition analysis of approved peptide therapeutics and diagnostics

• Published in: Drug discovery today Vol. 26; no. 6; pp. 1409 - 1419
• Main Authors: D’Aloisio, Vera, Dognini, Paolo, Hutcheon, Gillian A., Coxon, Christopher R.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.06.2021
• Subjects: Chemistry, Pharmaceutical - methods; Databases, Factual; Drug Approval; Drug Design; Humans; Peptides - administration & dosage; Peptides - chemistry; Peptides - pharmacology
• ISSN: 1359-6446; 1878-5832
• DOI: 10.1016/j.drudis.2021.02.019

•PepTherDia is a database containing 105 approved peptide pharmaceuticals.•86% of approved peptide therapeutics and diagnostics are natural or naturally-derived.•Bimodal distribution of peptide molar mass, with the large majority <2000g/mol.•Balance between polar and hydrophobic residues within the peptide structures.•46% of approved peptides are cyclic with 5 to 7 membered macrocycles being most common. As of 2020, there were >100 approved peptides with therapeutic or diagnostic applications. However, a complete database providing information on marketed peptides is not freely available, making the peptide chemists’ job of designing future peptide drug candidates challenging. Unlike the rules for small-molecule drugs, there is no general set of guidelines for designing a successful peptide-based drug. In this review, together with our freely available database (PepTherDia, http://peptherdia.herokuapp.com), we provide insights into what a successful peptide therapeutic or diagnostic agent looks like and lay the foundation for establishing a set of rules to help future medicinal chemists to design peptide candidates with increased approval rates. We describe a freely accessible database of approved peptide therapeutics and diagnostics, providing an overview of key structural and compositional trends to help guide the design of future peptide medicines.