Engineering "Antimicrobial Peptides" and Other Peptides to Modulate Protein-Protein Interactions in Cancer.

Abstract:

:Antimicrobial peptides (AMPs) are a class of peptides found across a wide array of organisms that play key roles in host defense. AMPs induce selective death in target cells and orchestrate specific or nonspecific immune responses. Many AMPs exhibit native anticancer activity in addition to antibacterial activity, and others have been engineered as antineoplastic agents. We discuss the use of AMPs in the detection and treatment of cancer as well as mechanisms of AMP-induced cell death. We present key examples of cathelicidins and transferrins, which are major AMP families. Further, we discuss the critical roles of protein-protein interactions (PPIs) in cancer and how AMPs are well-suited to target PPIs based on their unique drug-like properties not exhibited by small molecules or antibodies. While peptides, including AMPs, can have limited stability and bioavailability, these issues can be overcome by peptide backbone modification or cyclization (e.g., stapling) and by the use of delivery systems such as cellpenetrating peptides (CPPs), respectively. We discuss approaches for optimizing drug properties of peptide and peptidomimetic leads (modified peptides), providing examples of promising techniques that may be applied to AMPs. These molecules represent an exciting resource as anticancer agents with unique therapeutic advantages that can target challenging mechanisms involving PPIs. Indeed, AMPs are suitable drug leads for further development of cancer therapeutics, and many studies to this end are underway.

journal_name

Curr Top Med Chem

authors

Rubin SJS,Qvit N

doi

10.2174/1568026620666201021141401

subject

Has Abstract

pub_date

2020-01-01 00:00:00

pages

2970-2983

issue

32

eissn

1568-0266

issn

1873-4294

pii

CTMC-EPUB-110806

journal_volume

20

pub_type

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