Design, Synthesis, Biological Activity, and Structural Analysis of Lactam‐Constrained PTPRJ Agonist Peptides

Abstract

PTPRJ is a receptor-like protein tyrosine phosphatase mainly known for its antiproliferative and tumor-suppressive functions. PTPRJ dephosphorylates several growth factors and their receptors, negatively regulating cell proliferation and migration. We recently identified a disulfide-bridged nonapeptide, named PTPRJ-19 (H-[Cys-His-His-Asn-Leu-Thr-His-Ala-Cys]-OH), which activates PTPRJ, thereby causing cell growth inhibition and apoptosis of both cancer and endothelial cells. With the aim of replacing the disulfide bridge by a chemically more stable moiety, we have synthesized and tested a series of lactam analogues of PTPRJ-19. This replacement led to analogues with higher activity and greater stability than the parent peptide.

Rational design of the zonulin inhibitor AT1001 derivatives as potential anti SARS-CoV-2

“…Before proceeding with cell assays, the stability of the most active compound ( 4 ), determined by enzymatic experiments, was evaluated in aqueous solution [ 48 ]. Compound 4 was incubated at 25 °C and 37 °C in PBS buffer at pH 7.0.…”

Secondary Structure Stabilization of Macrocyclic Antimicrobial Peptides via Cross-Link Swapping

“…Side chain-to-side chain lactams have also been used with success in retaining activity as disulfide surrogates in various endogenous peptide hormones, such as human urotensin II, endothelin-1, and oxytocin, as well as in small disulfide-rich peptides, such as conotoxins and gomesin . Moreover, lactams between the side chains of C- and N-terminal residues have been used to enhance anticancer cell growth activity and improve stability in a peptide activator of protein tyrosine phosphatase receptor type J . In addition, a side chain-to-side chain lactam is featured in the melanocortin receptor agonist peptide medication bremelanotide (Vyleesi) for the treatment of premenopausal women with hypoactive sexual desire disorder …”

“…61 Moreover, lactams between the side chains of C-and N-terminal residues have been used to enhance anticancer cell growth activity and improve stability in a peptide activator of protein tyrosine phosphatase receptor type J. 62 In addition, a side chain-to-side chain lactam is featured in the melanocortin receptor agonist peptide medication bremelanotide (Vyleesi) for the treatment of premenopausal women with hypoactive sexual desire disorder. 63 Despite the significant application of side chain-to-side chain lactam constraints, few studies have examined influences on secondary structures other than helices.…”

Transcriptome analysis of discus fish (Symphysodon haraldi) skin and brain to identify genes involved in ‘milk’ secretion during parental care

“…Have study reported demonstrate the epidermal-type lipoxygenase. Aloxe3 is a potentially novel effector of the therapeutic fasting response (Sala et al, 2018). The discus fish will damage the skin tissue of the parents when pecking, and the content of Aloxe3 is reduced during the feeding period, which is consistent with Aloxe3 leads to a large amount of skin permeability and water loss leading to death after birth (Fournier et al, 2019).…”