Hybrid peptides constructed from RES-701-1, an endothelin B receptor antagonist, and endothelin; binding selectivity for endothelin receptors and their pharmacological activity

Shibata, Kenji; Suzawa, Toshiyuki; Ohno, Tetsuji; Yamada, Koji; Tanaka, Takeo; Tsukuda, Eiji; Matsuda, Yuzuru; Yamasaki, Motoo

doi:10.1016/s0968-0896(98)80020-5

Cited by 10 publications

(3 citation statements)

References 25 publications

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“…RES-701-1 is a potent endothelin B receptor (ET B )-selective antagonist, whereas both the acyclic and head-to-side-chain isomers of RES-701-1 have significantly reduced binding activities . However, Yamasaki and co-workers showed that a head-to-side-chain hybrid peptide combining the ring segment of RES-701-1 with a C-terminal fragment of endothelin-1 gave improved ET B binding activity, which improved further with the acyclic analog. , The findings from these studies support future efforts to evaluate the properties of nonthreaded acyclic and cyclic isomers of lasso peptides given their ease of access through chemical synthesis.…”

Section: Introductionmentioning

confidence: 66%

Nonthreaded Isomers of Sungsanpin and Ulleungdin Lasso Peptides Inhibit H1299 Cancer Cell Migration

Digal,

Samson,

Stevens

et al. 2023

ACS Chem. Biol.

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Lasso peptides are a structurally distinct class of biologically active natural products defined by their short sequences with impressively interlocked tertiary structures. Their characteristic peptide [1]rotaxane motif confers marked proteolytic and thermal resiliency, and reports on their diverse biological functions have been credited to their exceptional sequence variability. Because of these unique properties, taken together with improved technologies for their biosynthetic production, lasso peptides are emerging as a designable scaffold for peptide-based therapeutic discovery and development. Although the defined structure of lasso peptides is recognized for its remarkable properties, the role of the motif in imparting bioactivity is less understood. For example, sungsanpin and ulleungdin are natural lasso peptides that similarly exhibit encouraging cell migration inhibitory activities in A549 lung carcinoma epithelial cells, despite sharing only one-third of the sequence homology. We hypothesized that the shape of the lasso motif is beneficial for the preorganization of the conserved residues, which might be partially retained in variants lacking the threaded structure. Herein, we describe solid-phase peptide synthesis strategies to prepare acyclic, head-to-side chain (branched), and head-to-tail (macrocyclic) cyclic variants based on the sungsanpin (Sun) and ulleungdin (Uln) sequences. Proliferation assays and time-lapse cell motility imaging studies were used to evaluate the cell inhibitory properties of natural Sun compared with the synthetic Sun and Uln isomers. These studies demonstrate that the lasso motif is not a required feature to slow cancer cell migration and more generally show that these nonthreaded isomers can retain similar activity to the natural lasso peptide despite the differences in their overall structures.

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Section: Introductionmentioning

confidence: 66%

Nonthreaded Isomers of Sungsanpin and Ulleungdin Lasso Peptides Inhibit H1299 Cancer Cell Migration

Digal,

Samson,

Stevens

et al. 2023

ACS Chem. Biol.

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“…195 Further derivatives also showed antagonistic activity for the endothelin type A receptor. 196,197 These results nicely exemplify that natural products are promising lead structures for drug development.…”

Section: Opportunitiesmentioning

confidence: 75%

Opportunities and challenges of RiPP-based therapeutics

Pfeiffer,

Schröder,

Mordhorst

2024

Nat. Prod. Rep.

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“…Furthermore, the chemically-synthesized macrolactam ring from RES-701-1 was coupled to some bioactive peptides, thereby were combining activities and enhancing stabilities ( Shibata et al, 2003 ). Hybrid peptides of RES-701-1 as endothelin B receptor selective antagonist and endothelin could be applied as the promising therapeutic candidates against pancreatic adenocarcinoma ( Shibata et al, 1998 ; Cook et al, 2015 ). These indicate that segments of lasso peptides can be biologically active and useful even outside a lasso peptide topology.…”

Section: Potential Application Of Lasso Peptidesmentioning

confidence: 99%

Lasso Peptides: Heterologous Production and Potential Medical Application

Cheng

Hua

2020

Front. Bioeng. Biotechnol.

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Lasso peptides are natural products found in bacteria. They belong to a specific family of ribosomally-synthesized and posttranslationally-modified peptides with an unusual lasso structure. Lasso peptides possess remarkable thermal and proteolytic stability and various biological activities, such as antimicrobial activity, enzyme inhibition, receptor blocking, anticancer properties and HIV antagonism. They have promising potential therapeutic effects on gastrointestinal diseases, tuberculosis, Alzheimer's disease, cardiovascular disease, fungal infections and cancer. Lasso peptides with high stability have been shown to be good carriers for other bioactive peptides. These make them attractive candidates for pharmaceutical research. This review aimed to describe the strategies used for the heterologous production of lasso peptides. Also, it indicated their therapeutical potential and their capacity to use as an efficient scaffold for epitope grafting.

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Hybrid peptides constructed from RES-701-1, an endothelin B receptor antagonist, and endothelin; binding selectivity for endothelin receptors and their pharmacological activity

Cited by 10 publications

References 25 publications

Nonthreaded Isomers of Sungsanpin and Ulleungdin Lasso Peptides Inhibit H1299 Cancer Cell Migration

Nonthreaded Isomers of Sungsanpin and Ulleungdin Lasso Peptides Inhibit H1299 Cancer Cell Migration

Opportunities and challenges of RiPP-based therapeutics

Lasso Peptides: Heterologous Production and Potential Medical Application

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