Recent Trends in Cyclic Peptides as Therapeutic Agents and Biochemical Tools

Abstract

Notable progress has been made in the therapeutic and research applications of cyclic peptides since our previous review. New drugs based on cyclic peptides are entering the market, such as plecanatide, a cyclic peptide approved by the United States Food and Drug Administration in 2017 for the treatment of chronic idiopathic constipation. In this review, we discuss recent developments in stapled peptides, prepared with the use of chemical linkers, and bicyclic/tricyclic peptides with more than two rings. These have widespread applications for clinical and research purposes: imaging, diagnostics, improvement of oral absorption, enzyme inhibition, development of receptor agonist/antagonist, and the modulation of protein-protein interaction or protein-RNA interaction. Many cyclic peptides are expected to emerge as therapeutics and biochemical tools.

Characterization and Validation of Arg286 Residue of IL-1RAcP as a Potential Drug Target for Osteoarthritis

“…Peptide cyclization has been previously shown to dramatically improve peptide drug performance (Hu et al, 2004 ; Choi and Joo, 2020 ; Jing and Jin, 2020 ; Sohrabi et al, 2020 ), and more than 40 cyclic peptides have been approved for use in the clinic over the past decades (Jing and Jin, 2020 ). Cyclic peptides have distinct advantages over their acyclic counterparts targeting the same region: (1) greater binding affinity and selectivity toward target molecules due to their increased rigidity that reduces the entropy term in the Gibbs free energy equation, (2) resistance to enzymatic degradation because their rigid structure might prevent peptidases from accessing their cleavage site, and (3) increased membrane permeability in some cases (Choi and Joo, 2020 ). In this study, two of the best performing peptides, Peptides 1.2 and 4.2, were cyclic peptides.…”

<p>Applications of Graphene and Graphene Oxide in Smart Drug/Gene Delivery: Is the World Still Flat?</p>

“…Furthermore, therapeutic agents like anticancer drugs, proteins, gene and photosensitizers demonstrate a higher efficiency both in diagnosis and treatment of diseases when combined with graphene-based materials. [17][18][19] Recently, in a comprehensive study we could review and discuss developments in graphene and graphene oxide; properties, synthesis, and modifications. 10 In this review paper, we will investigate the most recent progress in biomedical usage of graphene and graphene-based materials, specifically targeted drug/gene delivery, delivery of antitumor drugs, smart and controlled stimuliresponsive drug release.…”

Bis-Lactam Peptide [i, i+4]-Stapling with α-Methylated Thialysines

“…Peptide stapling refers to the formation of an intra-chain macrocycle on a parent linear peptide, thereby inducing and stabilizing an α-helical conformation [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 ]. Stapled peptides have mostly been constructed with the [ i , i +4]- or the [ i , i +7]-stapling systems [ 9 ], and to a lesser extent with the [ i , i +11]- or the [ i , i +3]-stapling systems [ 10 , 11 , 12 , 13 ].…”

“…Stapled peptides have mostly been constructed with the [ i , i +4]- or the [ i , i +7]-stapling systems [ 9 ], and to a lesser extent with the [ i , i +11]- or the [ i , i +3]-stapling systems [ 10 , 11 , 12 , 13 ]. Due to its capability of potentially enhancing the proteolytic stability, cell permeability, and target binding affinity of a parent linear peptide, the peptide stapling technology has found extensive and successful use in chemical biology and medicinal chemistry [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 ]. While all-hydrocarbon stapling with the α-methyl-α-alkenyl α-amino acids including ( S )-2-(4′-pentenyl)alanine and ( R )-2-(7′-octenyl)alanine has been the prototypical and most extensively used peptide stapling strategy [ 9 ], it is interesting to note that all-hydrocarbon [ i , i +4]-stapling with ( S )-2-(4′-pentenyl)alanine (an α-disubstituted α-amino acid) on a linear peptide sequence derived from the BH3 domain of the BH3-only BCL-2 family member BID was found not to be more able to stabilize the α-helical conformation of the parent linear peptide than that with the corresponding α-monosubstituted amino acid (i.e., ( S )-2-(4′-pentenyl)glycine) [ 14 ].…”