From peptides to small molecules: an intriguing but intricated way to new drugs.
Curr Med Chem
; 20(31): 3803-17, 2013.
Article
in En
| MEDLINE
| ID: mdl-23895692
ABSTRACT
A variety of peptides active in biological pathways have been identified e.g. receptor antagonists or inhibitors of protein-protein interactions and several peptide or peptide-derived compounds are on the drug market or in clinical trials. Through the rational design or the combinatorial preparation and High-throughput screening of arrays of compounds, peptides play a pivotal role for the rapid identification of ligands, but, despite these favorable properties, they often present poorer bioavailability and lower metabolic stability respect to traditional drugs. The process of conversion of a peptide in a small molecule provides the reduction of the peptide to the minimum active sequence (MAS) testing truncated peptides from the C- and N- termini alternatively. Then the influence of individual amino acid on the biological activity is determined by systematically replacing each residue in the peptide with specific amino acids. After structure-activity relationship (SAR) of each amino acid in the sequence has been assessed, the bioactive conformational flexibility is reduced by introducing constraints at various positions. These features are used for the design of a pharmacophore model in which functional groups crucial for activity are pre-positioned. Here we propose a panoramic review of the common principles for the conversion of peptides into small organic molecules and the most interesting findings in peptide-based leads of the last decades.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Peptides
/
Drug Discovery
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Curr Med Chem
Journal subject:
QUIMICA
Year:
2013
Document type:
Article
Affiliation country:
Italy
Publication country:
AE
/
EMIRADOS ÁRABES UNIDOS
/
EMIRATOS ARABES UNIDOS
/
UNITED ARAB EMIRATES