Conjugation of thymopentin (TP5) with lipoamino acid residues increases the hydrolytic stability and preserves the biological activity.
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.
Pignatello
R
R
Dipartimento di Scienze Farmaceutiche, Città Universitaria, viale A. Doria, 6, 1-95125 Catania, Italy. r.pignatello@unict.it
Pecora
T M G
TM
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*
D000596:Amino Acids; D000970:Antineoplastic Agents; D008055:Lipids; D008081:Liposomes; D016305:Thymopentin