Exploring sequence space: harnessing chemical and biological diversity towards new peptide leads.
From their early roots in natural products, peptides now represent an expanding class of novel drugs. Their modular structures make them ideal candidates for pooled library screening approaches. Key technologies for library generation and screening, such as SICLOPPS, phage display and mRNA display, give unparalleled access to tight binding peptides. Through combination with genetic code reprogramming and chemical modifications, access to more natural product-like libraries, spanning non-canonical peptide space, is readily achievable. Recent advances in these fields enable introduction of diverse non-standard motifs, such as cyclisation and backbone methylations. Peptide discovery platforms now allow robust access to potent, highly functionalised peptides against virtually any protein of interest, with typical binding constants in the nanomolar range. Application of these optimised platforms in a drug discovery setting has the potential to significantly accelerate identification of new leads.
Department of Chemistry, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Richard
R
Obexer
Department of Chemistry, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Louise J
LJ
Walport
Department of Chemistry, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. Electronic address: hsuga@chem.s.u-tokyo.ac.jp.
Hiroaki
H
Suga
D000595:Amino Acid Sequence; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology
D010455:Peptides