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

[Display omitted] •A novel Pt(II) complex conjugated to a transferrin binding peptide was characterized.•The Pt(II) coordination was studied by mass spectrometry and NMR techniques.•Cytotoxicity in panel of nine cells was evaluated.•DNA binding and albumin binding was evaluated.•The synthetic method...

Full description

Saved in:

Bibliographic Details
Published in:	Inorganica Chimica Acta Vol. 511; p. 119811
Main Authors:	Teles, Catherine M., Antunes, Víctor U., Cardoso, Raquel S., Candido, Tuany Z., Lima, Carmen S.P., Ruiz, Ana Lúcia T.G., Juliano, Maria A., Favaro, Denize C., Abbehausen, Camilla
Format:	Journal Article
Language:	English
Published:	Amsterdam Elsevier B.V 01-10-2020 Elsevier Science Ltd
Subjects:	Binding Biomolecules Conjugation Coordination Glycine Hormones Ions Mass spectrometry NMR Nuclear magnetic resonance Peptides Platinum Platinum conjugates Receptors Selectivity Serum albumin Solid phases Solid-phase peptide synthesis Transferrin Transferrin receptor binding peptide Platinum conjugates Solid-phase peptide synthesis Transferrin receptor binding peptide
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	[Display omitted] •A novel Pt(II) complex conjugated to a transferrin binding peptide was characterized.•The Pt(II) coordination was studied by mass spectrometry and NMR techniques.•Cytotoxicity in panel of nine cells was evaluated.•DNA binding and albumin binding was evaluated.•The synthetic methodology for preparation of metallopeptides was discussed. 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.
ISSN:	0020-1693 1873-3255
DOI:	10.1016/j.ica.2020.119811