Cyclizing Painkillers: Development of Backbone-Cyclic TAPS Analogs.

TAPS backbone cyclization cycloscan peripheral painkiller reductive alkylation

Journal

Frontiers in chemistry
ISSN: 2296-2646
Titre abrégé: Front Chem
Pays: Switzerland
ID NLM: 101627988

Informations de publication

Date de publication:
2020
Historique:
received: 04 02 2020
accepted: 07 10 2020
entrez: 7 12 2020
pubmed: 8 12 2020
medline: 8 12 2020
Statut: epublish

Résumé

Painkillers are commonly used medications. Native peptide painkillers suffer from various pharmacological disadvantages, while small molecule painkillers like morphine are highly addictive. We present a general approach aimed to use backbone-cyclization to develop a peptidomimetic painkiller. Backbone-cyclization was applied to transform the linear peptide Tyr-Arg-Phe-Sar (TAPS) into an active backbone-cyclic peptide with improved drug properties. We designed and synthesized a focused backbone-cyclic TAPS library with conformational diversity, in which the members of the library have the generic name TAPS c(n-m) where n and m represent the lengths of the alkyl chains on the nitrogens of Gly and Arg, respectively. We used a combined screening approach to evaluate the pharmacological properties and the potency of the TAPS c(n-m) library. We focused on an

Identifiants

pubmed: 33282822
doi: 10.3389/fchem.2020.532577
pmc: PMC7689096
doi:

Types de publication

Journal Article

Langues

eng

Pagination

532577

Informations de copyright

Copyright © 2020 Talhami, Swed, Hess, Ovadia, Greenberg, Schumacher-Klinger, Rosenthal, Shalev, Hurevich, Lazarovici, Hoffman and Gilon.

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Auteurs

Alaa Talhami (A)

Department of Organic Chemistry, Institute of Chemistry, The Hebrew University of Jerusalem, Jerusalem, Israel.

Avi Swed (A)

School of Pharmacy, Institute for Drug Research, The Hebrew University of Jerusalem, Jerusalem, Israel.

Shmuel Hess (S)

Meytav Technologies Incubator, Kiryat Shmona, Israel.

Oded Ovadia (O)

School of Pharmacy, Institute for Drug Research, The Hebrew University of Jerusalem, Jerusalem, Israel.

Sarit Greenberg (S)

School of Pharmacy, Institute for Drug Research, The Hebrew University of Jerusalem, Jerusalem, Israel.

Adi Schumacher-Klinger (A)

School of Pharmacy, Institute for Drug Research, The Hebrew University of Jerusalem, Jerusalem, Israel.

David Rosenthal (D)

Department of Organic Chemistry, Institute of Chemistry, The Hebrew University of Jerusalem, Jerusalem, Israel.

Deborah E Shalev (DE)

Department of Pharmaceutical Engineering, Azrieli College of Engineering Jerusalem, Jerusalem, Israel.
Wolfson Centre for Applied Structural Biology, The Hebrew University of Jerusalem, Jerusalem, Israel.

Mattan Hurevich (M)

Department of Organic Chemistry, Institute of Chemistry, The Hebrew University of Jerusalem, Jerusalem, Israel.

Philip Lazarovici (P)

School of Pharmacy, Institute for Drug Research, The Hebrew University of Jerusalem, Jerusalem, Israel.

Amnon Hoffman (A)

School of Pharmacy, Institute for Drug Research, The Hebrew University of Jerusalem, Jerusalem, Israel.

Chaim Gilon (C)

Department of Organic Chemistry, Institute of Chemistry, The Hebrew University of Jerusalem, Jerusalem, Israel.

Classifications MeSH