Mannose 6-phosphate receptor targeting and its applications in human diseases.

Abstract:

:The cation-independent mannose 6-phosphate receptor is a multifunctional protein which binds at the cell surface to two distinct classes of ligands, the mannose 6-phosphate (M6P) bearing proteins and IGF-II. Its major function is to bind and transport M6P-enzymes to lysosomes, but it can also modulate the activity of a variety of extracellular M6P-glycoproteins (i.e., latent TGFbeta precursor, urokinase-type plasminogen activator receptor, Granzyme B, growth factors, Herpes virus). The purpose of this review is to highlight the synthesis and potential use of high affinity M6P analogues able to target this receptor. Several M6P analogues with phosphonate, carboxylate or malonate groups display a higher affinity and a stronger stability in human serum than M6P itself. These derivatives could be used to favour the delivery of specific therapeutic compounds to lysosomes, notably in enzyme replacement therapies of lysosomal diseases or in neoplastic drug targeting. In addition, their potential applications in preventing clinical disorders, which are associated with the activities of other M6P-proteins involved in wound healing, cell growth or viral infection, will be discussed.

journal_name

Curr Med Chem

authors

Gary-Bobo M,Nirdé P,Jeanjean A,Morère A,Garcia M

doi

10.2174/092986707782794005

subject

Has Abstract

pub_date

2007-01-01 00:00:00

pages

2945-53

issue

28

eissn

0929-8673

issn

1875-533X

journal_volume

14

pub_type

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