Peptides and Peptide Derivatives as G‐Quadruplex Targeting Ligands: A Brief Review

In this review, our discussion mainly focused on structurally diverse peptides (linear, cyclic, branch, conjugated) reported in literature between the years 2000 to 2022 having potential to target non-canonical G-quadruplex (G4) nucleic acid structures and its biomedical applications.

Abstract

Genomic DNA adopts B-form canonically. Besides, the oligonucleotides can adopt various non-canonical secondary structures. These are hairpins, cruciforms, triplexes, quadruplexes (G4), i-motifs etc. G4s are usually formed by the guanine rich oligonucleotides and are found in both DNA and RNA. G4s are more frequently distributed in telomeres, promoter oncogenes, immunoglobulin switch regions, ribosomal DNA etc. Recently, it has been established that G4s are intriguingly connected with different human diseases including cancer. Stabilization of G4s by designed molecules or drugs impedes the transcription of several oncogenes and also creates encumbrance to the telomere biogenesis which is very important in impediment of cancer. G4 is treated as an important molecular target in the discovery of anti-cancer drugs. Among the G4 targeting molecules, peptides draw sincere attention due to its small size, simple synthetic methodology, low cytotoxicity and cellular permeability. In this review, our main discussion revolves around the formation of G4, distribution of G4 in genome, structurally diverse peptides (linear, cyclic, branch, conjugated) having potential to target G4 structures and its future perspectives.

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