title: Conjugation of thymopentin (TP5) with lipoamino acid residues increases the hydrolytic stability and preserves the biological activity.
abstract: Three conjugates of thymopentin (TP5), an oligopeptide derived from the thymic hormone thymopoietin, with lipoamino acid (LAAs) have been obtained by solid-phase peptide synthesis. Both linear and dendrimer structures have been prepared to achieve enhanced lipophilicity. After incubation in foetal calf serum the lipophilic conjugates showed a higher stability to hydrolysis with respect to the parent drug. In a preliminary in vitro biological assay, LAA conjugates showed the ability to retain or improve the growth inhibitory activity of the parent peptide against a human lymphoblastoid cell line. The interaction of the prepared conjugates with 1,2-L-alpha-dimiristoylphosphatidylcholine multilamellar liposomes, chosen as a biological membrane model, was studied. The higher lipophilicity of TP5 conjugates was reflected in a better penetration through phospholipid bilayers, whose thermal behaviour was altered in a concentration-dependent way. Such enhanced affinity of TP5-LAA conjugates for this membrane model could anticipate a better interaction with cell membranes and, ultimately, an improved biological activity of compounds compared with the parent pentapeptide.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Città Universitaria, viale A. Doria, 6, 1-95125 Catania, Italy. r.pignatello@unict.it
authors.forename: R
authors.initials: R
authors.lastname: Pignatello
authors.forename: T M G
authors.initials: TM
authors.lastname: Pecora
mesh_terms: D000596:Amino Acids / Q000737:chemistry* / Q000494:pharmacology*; D016880:Anisotropy; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002152:Calorimetry, Differential Scanning; D002460:Cell Line; D045744:Cell Line, Tumor; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D004058:Diffusion; D004355:Drug Stability; D006801:Humans; D006868:Hydrolysis; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000188:drug therapy / Q000473:pathology; D008055:Lipids / Q000737:chemistry* / Q000494:pharmacology*; D008081:Liposomes; D016305:Thymopentin / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000596:Amino Acids; D000970:Antineoplastic Agents; D008055:Lipids; D008081:Liposomes; D016305:Thymopentin