Academic Journal
Sequence Inversion Dictates the Antiproliferative Activity of Bidirectional Tryptophan-Containing Dipeptide Libraries.
| Τίτλος: | Sequence Inversion Dictates the Antiproliferative Activity of Bidirectional Tryptophan-Containing Dipeptide Libraries. |
|---|---|
| Συγγραφείς: | Díaz JB; BioLab, Instituto Universitario de Bio-Orgánica Antonio González, Universidad de La Laguna, La Laguna, Spain., Khan AN; BioLab, Instituto Universitario de Bio-Orgánica Antonio González, Universidad de La Laguna, La Laguna, Spain., González-Bakker A; BioLab, Instituto Universitario de Bio-Orgánica Antonio González, Universidad de La Laguna, La Laguna, Spain., Padrón JM; BioLab, Instituto Universitario de Bio-Orgánica Antonio González, Universidad de La Laguna, La Laguna, Spain. |
| Πηγή: | Journal of peptide science : an official publication of the European Peptide Society [J Pept Sci] 2026 Oct; Vol. 32 (10), pp. e70128. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: John Wiley & Sons Country of Publication: England NLM ID: 9506309 Publication Model: Print Cited Medium: Internet ISSN: 1099-1387 (Electronic) Linking ISSN: 10752617 NLM ISO Abbreviation: J Pept Sci Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Chichester, West Sussex, UK : John Wiley & Sons, c1995- |
| Ιατρικοί όροι (MeSH): | Dipeptides*/chemistry , Dipeptides*/pharmacology , Dipeptides*/chemical synthesis , Tryptophan*/chemistry , Tryptophan*/pharmacology , Antineoplastic Agents*/pharmacology , Antineoplastic Agents*/chemistry , Antineoplastic Agents*/chemical synthesis , Peptide Library*, Cell Proliferation/drug effects ; Humans ; Structure-Activity Relationship ; Drug Screening Assays, Antitumor ; Cell Line, Tumor |
| Περίληψη: | Two complementary series of novel tryptophan-derived dipeptides (Trp-X and X-Trp) were designed and synthesized to systematically evaluate how backbone sequence inversion alters chemical accessibility and in vitro antineoplastic profiles against a human solid tumor cell line panel (A549, HeLa, MIA PaCa-2, SW1573, T-47D, and WiDr). Reversing the peptide connectivity revealed prominent sequence-dependent chemical reactivities and biological variations. Steric repulsion at the β-carbon limited basic hydrolysis during X-Trp precursor assembly, whereas the Trp-X series allowed straightforward chemical couplings. Phenotypic screening demonstrated that the Trp-X configuration is biologically superior to the X-Trp layout. The conformationally restricted L-proline conjugate (Trp-Pro) emerged as the lead architecture, exhibiting consistent, single-digit sub-micromolar growth inhibition across all histotypes (GI (© 2026 The Author(s). Journal of Peptide Science published by European Peptide Society and John Wiley & Sons Ltd.) |
| References: | Respir Investig. 2026 Sep;64(5):101492. (PMID: 42508346) Amino Acids. 2015 Aug;47(8):1527-32. (PMID: 25900811) Ther Drug Monit. 2020 Feb;42(1):20-32. (PMID: 31259881) J Org Chem. 1997 Apr 4;62(7):2292-2297. (PMID: 11671547) Pharmacol Ther. 2009 Jan;121(1):29-40. (PMID: 18992769) Exp Mol Med. 2023 Jun;55(6):1099-1109. (PMID: 37258584) Pediatr Blood Cancer. 2024 Nov;71(11):e31247. (PMID: 39120434) Molecules. 2024 Oct 09;29(19):. (PMID: 39407697) Org Lett. 2006 May 11;8(10):2183-6. (PMID: 16671812) Nat Protoc. 2006;1(3):1112-6. (PMID: 17406391) J Am Chem Soc. 2022 Jan 12;144(1):288-296. (PMID: 34968060) Lung Cancer Manag. 2023 May 23;12(2):LMT59. (PMID: 37287941) J Natl Cancer Inst. 1991 Jun 5;83(11):757-66. (PMID: 2041050) Anal Biochem. 2012 Feb 15;421(2):767-9. (PMID: 22230286) Curr Pharm Des. 2010;16(28):3185-203. (PMID: 20687878) Chem Biol Drug Des. 2026 Jun;107(6):e70330. (PMID: 42313430) Tetrahedron Lett. 2021 Jun 8;73:. (PMID: 34176980) |
| Grant Information: | PID2021-123059OB-I00 MCIN; AEI |
| Contributed Indexing: | Keywords: anticancer drugs; antiproliferative activity; peptide sequence inversion; phenotypic screening; structure–activity relationships (SAR); tryptophan dipeptides |
| Substance Nomenclature: | 0 (Dipeptides) 8DUH1N11BX (Tryptophan) 0 (Antineoplastic Agents) 0 (Peptide Library) |
| Entry Date(s): | Date Created: 20260916 Date Completed: 20260916 Latest Revision: 20260919 |
| Update Code: | 20260919 |
| PubMed Central ID: | PMC13581466 |
| DOI: | 10.1002/psc.70128 |
| PMID: | 42749494 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1099-1387 |
|---|---|
| DOI: | 10.1002/psc.70128 |