Functionalization of new anticancer Pt(II) complex with transferrin receptor binding peptide

Autor(es)

Teles, Catherine M. ^[1] ; Antunes, Victor U. ^[1] ; Cardoso, Raquel S. ^[2] ; Candido, Tuany Z. ^[3] ; Lima, Carmen S. P. ^[3] ; Ruiz, Ana Lucia T. G. ^[2] ; Juliano, Maria A. ^[4] ; Favaro, Denize C. ^[1] ; Abbehausen, Camilla ^[1]

Afiliação do(s) autor(es)

^[1] Univ Estadual Campinas, Inst Chem, UNICAMP, POB 6154, BR-13083970 Campinas, SP - Brazil

^[2] Univ Estadual Campinas, Fac Pharmaceut Sci, UNICAMP, BR-13083871 Campinas, SP - Brazil

^[3] Univ Estadual Campinas, Fac Med Sci, UNICAMP, BR-13083970 Campinas, SP - Brazil

^[4] Univ Fed Sao Paulo, UNIFESP, Escola Paulista Med, BR-04063062 Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Inorganica Chimica Acta; v. 511, OCT 1 2020.
• Citações Web of Science: 0

Resumo

One strategy to improve the selectivity of metallocompounds is to functionalize them by conjugation with biomolecules as folate, hormones, and peptides. In this work, we describe the conjugation of a transferrin re-ceptor binding peptide of sequence HAIYPHRH to a Pt(II) bis(2-pyridylmethyl)glycine complex. The complex was fully characterized by mass spectrometry and 1D and 2D NMR. Among several synthetic strategies, the preparation of bis-(2-pyridylmethyl)glycyl-NH-HAIYPHRH by solid-phase peptide synthesis, its purification by HPLC, followed by the coordination of Pt(II) was the successful method. The metal coordination was studied by H-1 NMR and H-1 -N-15 HSQC. The results show the metal ion interacts by fast exchange reaction with the two terminal histidines and slow exchange with bis(2-pyridylmethyl)glycine moiety. The compounds presented in-hibition of growth for renal cancer cells; therefore, it is not an effect of the peptide as the precursor, {[}PtCl(bis(2-pyridylmethyl)glycine)], presents similar GI(50). The peptide-Pt(II) complex presents a high binding constant with serum albumin and demonstrated to bind covalently to DNA by electrophoretic mobility assays. The work re-presents a complete description of the coordination of platinum in this system and demonstrates the challenges to develop new metallopeptides. (AU)

• Processo FAPESP: 19/16904-2 - Metalofármacos direcionados a alvos específicos para o tratamento de leishmaniose
• Beneficiário: Camilla Abbehausen
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 16/07729-4 - Complexos metálicos de ouro, paládio e prata no tratamento do carcinoma de células escamosas de pele
• Beneficiário: Tuany Zambroti Cândido
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 12/50191-4 - Síntese, estudo cinético e aplicações de substratos e inibidores de enzimas proteolíticas
• Beneficiário: Maria Aparecida Juliano
• Modalidade de apoio: Auxílio à Pesquisa - Temático