Strategies to Enhance Metabolic Stabilities

Khatri, B and Nuthakki, VR and Chatterjee, J (2019) Strategies to Enhance Metabolic Stabilities. [Book Chapter]

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Abstract

Macrocyclic peptides are a unique class of molecules that display a relatively constrained peptidic backbone as compared to their linear counterparts leading to the defined 3-D orientation of the constituent amino acids (pharmacophore). Although they are attractive candidates for lead discovery owing to the unique conformational features, their peptidic backbone is susceptible to proteolytic cleavage in various biological fluids that compromise their efficacy. In this chapter we review the various classical and contemporary chemical and biological approaches that have been utilized to combat the metabolic instability of macrocyclic peptides. We note that any chemical modification that helps in providing either local or global conformational rigidity to these macrocyclic peptides aids in improving their metabolic stability typically by slowing the cleavage kinetics by the proteases.

Item Type:	Book Chapter
Publication:	Methods in Molecular Biology
Publisher:	Humana Press Inc.
Additional Information:	The copyright for this article belongs to Humana Press Inc.
Keywords:	cyclopeptide; macrocyclic peptide; proteinase; unclassified drug; conotoxin; cyclopeptide; cyclotide; peptide hormone, body fluid; chemical modification; high throughput screening; metabolic stability; protein conformation; protein degradation; protein secondary structure; rigidity; alpha helix; beta sheet; chemistry; conformation; cyclization; kinetics; metabolism; methylation; oral drug administration, Administration, Oral; Conotoxins; Cyclization; Cyclotides; High-Throughput Screening Assays; Kinetics; Methylation; Molecular Conformation; Peptide Hormones; Peptides, Cyclic; Protein Conformation, alpha-Helical; Protein Conformation, beta-Strand
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited:	22 Nov 2022 09:39
Last Modified:	22 Nov 2022 09:39
URI:	https://eprints.iisc.ac.in/id/eprint/77959

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