Functionalization of new anticancer Pt(II) complex with transferrin receptor binding peptide
| Autor: | Victor U. Antunes, Maria A. Juliano, Tuany Z. Candido, Catherine Morais Teles, Denize C. Favaro, Camilla Abbehausen, Ana Lúcia Tasca Gois Ruiz, Raquel Soares Cardoso, Carmen Silvia Passos Lima |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
chemistry.chemical_classification
010405 organic chemistry Chemistry Peptide 010402 general chemistry 01 natural sciences Combinatorial chemistry Binding constant 0104 chemical sciences Inorganic Chemistry chemistry.chemical_compound Transferrin receptor binding Glycine Materials Chemistry Peptide synthesis Moiety Physical and Theoretical Chemistry Two-dimensional nuclear magnetic resonance spectroscopy Heteronuclear single quantum coherence spectroscopy |
| Zdroj: | Inorganica Chimica Acta. 511:119811 |
| ISSN: | 0020-1693 |
| Popis: | 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 receptor 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 1H NMR and 1H-15N 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 inhibition 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 GI50. 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 represents a complete description of the coordination of platinum in this system and demonstrates the challenges to develop new metallopeptides. |
| Databáze: | OpenAIRE |
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