Molecular Diversity

, Volume 22, Issue 2, pp 259–267 | Cite as

Exploring the chemical space of peptides for drug discovery: a focus on linear and cyclic penta-peptides

  • Bárbara I. Díaz-Eufracio
  • Oscar Palomino-Hernández
  • Richard A. Houghten
  • José L. Medina-FrancoEmail author
Original Article


Peptide and peptide-like structures are regaining attention in drug discovery. Previous studies suggest that bioactive peptides have diverse structures and may have physicochemical properties attractive to become hit and lead compounds. However, chemoinformatic studies that characterize such diversity are limited. Herein, we report the physicochemical property profile and chemical space of four synthetic linear and cyclic combinatorial peptide libraries. As a case study, the analysis was focused on penta-peptides. The chemical space of the peptide and N-methylated peptides libraries was compared to compound data sets of pharmaceutical relevance. Results indicated that there is a major overlap in the chemical space of N-methylated cyclic peptides with inhibitors of protein–protein interactions and macrocyclic natural products available for screening. Also, there is an overlap between the chemical space of the synthetic peptides with peptides approved for clinical use (or in clinical trials), and to other approved drugs that are outside the traditional chemical space. Results further support that synthetic penta-peptides are suitable compounds to be used in drug discovery projects.


Cheminformatics Chemical space Combinatorial chemistry Protein–protein inhibitors Small molecules Synthetic peptides 



B.I.D.-E. and O.P. acknowledges Consejo Nacional de Ciencia y Tecnología (CONACyT) for Scholarships Number 620289 and 606003, respectively. This work was supported by the Programa de Apoyo a la Investigación y el Posgrado (PAIP) Grant 5000-9163, Facultad de Química, UNAM. This work is dedicated to the loving memory of Nicolás Medina Sandoval.

Supplementary material

11030_2018_9812_MOESM1_ESM.pdf (388 kb)
Supplementary material 1 (pdf 387 KB)
11030_2018_9812_MOESM2_ESM.cdx (29 kb)
Supplementary material 2 (cdx 29 KB)


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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.School of Chemistry, Department of PharmacyUniversidad Nacional Autónoma de MéxicoMexico CityMexico
  2. 2.Torrey Pines Institute for Molecular StudiesPort St. LucieUSA

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