Open AccessRecent advances in the synthesis of C-terminally modified peptides
Author(s) -
Christine A. Arbour,
Lawrence G. Mendoza,
Jennifer L. Stockdill
Publication year - 2020
Publication title -
organic and biomolecular chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.923
H-Index - 146
eISSN - 1477-0539
pISSN - 1477-0520
DOI - 10.1039/d0ob01417f
Subject(s) - chemistry , peptide , cleavage (geology) , combinatorial chemistry , native chemical ligation , membrane permeability , surface modification , biochemistry , chemical synthesis , in vitro , membrane , geotechnical engineering , fracture (geology) , engineering
C-Terminally modified peptides are important for the development and delivery of peptide-based pharmaceuticals because they impact peptide activity, stability, hydrophobicity, and membrane permeability. Additionally, the vulnerability of C-terminal esters to cleavage by endogenous esterases makes them excellent pro-drugs. Methods for post-SPPS C-terminal functionalization potentially enable access to libraries of modified peptides, facilitating tailoring of their solubility, potency, toxicity, and uptake pathway. Apparently minor structural changes can significantly impact the binding, folding, and pharmacokinetics of the peptide. This review summarizes developments in chemical methods for C-terminal modification of peptides published since the last review on this topic in 2003.