Carrier design: biodistribution of branched polypeptides with a poly(L-lysine) backbone

Abstract

The biodistribution has been examined in mice of a range of synthetic branched polypeptides which are based on a polylysine backbone but which differ in ionic charge, side-chain structure, and molecular size. Polycationic polypeptides, regardless of their size or primary structure at the branches, were cleared rapidly from the circulation, the liver being the major site of clearance. Polypeptides with glutamic acid in the side chain, which would be amphoteric under physiological conditions, showed a significantly prolonged blood survival, and this was seen with polypeptides in the range of molecular weights of 46,000 up to 213,000. Such polypeptides provide a useful system with which to investigate the effect of structural parameters on the pharmacokinetic properties of carrier molecules and would allow the selection of candidate carriers for a variety of uses.

Interaction of branched chain polymeric polypeptides with phospholipid model membranes

“…cluding analysis of solution conformation, 12 evaluation of in vitro cytotoxicity, 13 immunoreactivity, 12,13 and biodistribution 14 -various bioconjugates were Promising results have been reported concerning the prepared. In these constructs either antitumor agents use of polymeric compounds in experimental cancer (daunomycin, methotrexate, GnRH antagonist), 15-17 chemotherapy 1 or in human multiple sclerosis.…”

The Influence of Branched Polypeptide Carriers on the Immunogenicity of Predicted Epitopes of HSV‐1 Glycoprotein D

“…Both approaches in most cases requires also the addition of an efficient adjuvant [35,36] Synthetic branched polypeptides have been introduced as effective carriers for B cell determinants by the pioneering work of Sela and co-workers [12-16, 37, 38]. A structurally simplified family of synthetic branched polypeptides has been developed by Hudecz et al [19] and these molecules have been extensively characterized by their chemical and biological properties [17,[39][40][41][42]. In this study the efficacy of two of these macromolecules as carriers for previously identified HSV-1 gD B cell epitopes was investigated.…”

Artificial Carriers: A Strategy for Constructing Antigenic/Immunogenic Conjugates

“…4) [52][53][54]. Emphasis was given on the structural characterization of these polymeric polypeptides, such as chemical analysis, size, primary structure (enantiomer composition and length distribution of the side chains) and solution conformation in relation to the biological activities attributed to the carrier function, immunoreactivity, immunomodulatory potential, biodegradation, in vitro cytotoxicity and biodistribution [55][56][57][58].…”