Abstract:
:Due to its remarkably long half-life, together with its wide in vivo distribution and its lack of enzymatic or immunological functions, human serum albumin (HSA) represents an optimal carrier for therapeutic peptides/proteins aimed at interacting with cellular or molecular components of the vascular and interstitial compartments. As an example, we designed a genetically engineered HSA-CD4 hybrid aimed at specifically blocking the entry of the human immunodeficiency virus into CD4+ cells. In contrast with CD4, HSA-CD4 is correctly processed and efficiently secreted by Kluyveromyces yeasts. In addition, its CD4 moiety exhibits binding and antiviral in vitro properties similar to those of soluble CD4. Finally, the elimination half-life of HSA-CD4 in a rabbit experimental model is comparable to that of control HSA and 140-fold higher than that of soluble CD4. These results indicate that the genetic fusion of bioactive peptides to HSA is a plausible approach toward the design and recovery of secreted therapeutic HSA derivatives with appropriate pharmacokinetic properties.
journal_name
Proc Natl Acad Sci U S Aauthors
Yeh P,Landais D,Lemaître M,Maury I,Crenne JY,Becquart J,Murry-Brelier A,Boucher F,Montay G,Fleer Rdoi
10.1073/pnas.89.5.1904keywords:
subject
Has Abstract,Author List Incompletepub_date
1992-03-01 00:00:00pages
1904-8issue
5eissn
0027-8424issn
1091-6490journal_volume
89pub_type
杂志文章abstract::Although the role of liganded nuclear receptors in mediating coactivator/corepressor exchange is well-established, little is known about the potential regulation of chromosomal organization in the 3-dimensional space of the nucleus in achieving integrated transcriptional responses to diverse signaling events. Here, we...
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