Recent advances in the synthesis of C-terminally modified peptides

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 th...

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Bibliographic Details
Published in:Organic & biomolecular chemistry 2020-09, Vol.18 (37), p.7253-7272
Main Authors: Arbour, Christine A, Mendoza, Lawrence G, Stockdill, Jennifer L
Format: Article
Language:English
Subjects:
Esterases
Esters
Humans
Hydrophobicity
Membrane permeability
Peptides
Peptides - chemical synthesis
Peptides - chemistry
Pharmacokinetics
Toxicity
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Summary: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. A go-to compilation of recent strategies to access C-terminally modified peptides contextualized by a discussion of the major synthetic challenges that have historically hampered progress in this area.
ISSN:1477-0520
1477-0539
1477-0539
DOI:10.1039/d0ob01417f