Title

Structure-Activity Investigations Of Polyamine-Anthracene Conjugates And Their Uptake Via The Polyamine Transporter

Keywords

Anthracene; Cytotoxicity; Polyamine; Transport

Abstract

A series of polyamine conjugates were synthesized and evaluated for their ability to target the polyamine transporter (PAT) in two Chinese hamster ovary (CHO) cell lines (PAT-active CHO and PAT-inactive CHOMG). This systematic study identified salient features of the polyamine architecture required to target and enter cells via the PAT. Indeed, the separation of charges, the degree of N-alkylation, and the spacer unit connecting the N1-terminus to the appended cytotoxic component (anthracene) were found to be key contributors to optimal delivery via the PAT. Using the CHO screen, the homospermidine motif (e.g., 4,4-triamine) was identified as a polyamine vector, which could enable the selective import of large N1-substituents (i.e., naphthylmethyl, anthracenylmethyl and pyrenylmethyl), which were cytotoxic to cells. The cell selectivity of this approach was demonstrated in B-16 murine melanoma cells and normal melanocytes (Mel-A). Three polyamine areas (recognition and transport, vesicle sequestration and polyamine-target interactions) were identified for future research. © 2007 Springer-Verlag.

Publication Date

8-1-2007

Publication Title

Amino Acids

Volume

33

Issue

2

Number of Pages

305-313

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.1007/s00726-007-0527-y

Socpus ID

34547678624 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/34547678624

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