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. |
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| 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.) |
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| 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 |
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