The recombinant third domain of human alpha-fetoprotein retains the antiestrotrophic activity found in the full-length molecule

Festin, Stephen

doi:10.1016/s0304-4165(99)00030-6

Cited by 23 publications

(23 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…AFPep was derived from the naturally occurring protein α-fetoprotein (AFP) [16, 29, 30] which is produced during fetal development [4, 5, 21] and which exhibits anti-oncogenic activity [23]. AFP is reported to be the primary agent responsible for a decreased incidence of breast cancer in populations of women who have experienced a full-term pregnancy compared to the nulliparous population [22, 24, 37].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Design and synthesis of biologically active peptides: A ‘tail’ of amino acids can modulate activity of synthetic cyclic peptides

et al. 2011

View full text Add to dashboard Cite

In earlier work, we synthesized a cyclic 9-amino acid peptide (AFPep, cyclo[EKTOVNOGN]) and showed it to be useful for prevention and therapy of breast cancer. In an effort to explore the structure-function relationships of AFPep, we have designed analogs that bear a short ‘tail’ (one or two amino acids) attached to the cyclic peptide distal to its pharmacophore. Analogs that bore a tail of either one or two amino acids, either of which had a hydrophilic moiety in the side chain (example: cyclo[EKTOVNOGN]FS) exhibited greatly diminished biological activity (inhibition of estrogen-stimulated uterine growth) relative to AFPep. Analogs that bore a tail of either one or two amino acids which had hydrophobic (aliphatic or aromatic) side chains (example: cyclo[EKTOVNOGN]FI) retained (or had enhanced) growth inhibition activity. Combining in the same biological assay a hydrophilic-tailed analog with either AFPep or a hydrophobic-tailed analog resulted in decreased activity relative to that for AFPep or for the hydrophobic-tailed analog alone, suggesting that hydrophilic-tailed analogs are binding to a biologically active receptor. An analog with a disrupted pharmacophore (cyclo[EKTOVGOGN]) exhibited little or no growth inhibition activity. An analog with a hydrophilic tail and a disrupted pharmacophore (cyclo[EKTOVGOGN]FS) exhibited no growth inhibition activity of its own and did not affect the activity of a hydrophobic-tailed analog, but enhanced the growth inhibition activity of AFPep. These results are discussed in the context of a two-receptor model for binding of AFPep and ring-and-tail analogs. We suggest that tails on cyclic peptides may comprise a useful method to enhance diversity of peptide design and specificity of ligand-receptor interactions.

show abstract

Section: Discussionmentioning

confidence: 99%

“…[16]. In this screening assay, inhibition of estrogen-stimulated uterine growth is closely correlated with inhibition of estrogen-stimulated tumor growth in xenograft assays.…”

Section: Methodsmentioning

confidence: 99%

Design and synthesis of biologically active peptides: A ‘tail’ of amino acids can modulate activity of synthetic cyclic peptides

et al. 2011

View full text Add to dashboard Cite

show abstract

“…Domain III yielded anti-uterotrophic dose-response curves similar to full-length AFP (49), whereas the N-terminal half of the protein had little or no anti-uterotrophic activity. Continued efforts to parse the active fragment employed peptide synthesis, beginning with the synthesis of large peptide fragments (51).…”

Section: Development Of Afpepmentioning

confidence: 95%

“…That such a site existed was supported by difference spectroscopy data (49) which indicated that a conformational change in the structure of the molecule occurred in the presence of estrogen and that change actually generated increased anti-estrogenicity of AFP (an increase that could not be explained by binding and sequestration of estrogen by AFP; refs. 5,49).…”

Section: Development Of Afpepmentioning

confidence: 99%

“…Rather than working with full-length AFP (39), Festin and colleagues parsed the molecule by expressing domains and subdomains (49) and showed that the anti-estrotrophic activity of AFP was contained in the C-terminal third of the protein, a 23,000 MW fragment known as domain III (50). Domain III yielded anti-uterotrophic dose-response curves similar to full-length AFP (49), whereas the N-terminal half of the protein had little or no anti-uterotrophic activity.…”

Section: Development Of Afpepmentioning

confidence: 99%

See 1 more Smart Citation

Development of an Active Site Peptide Analog of α-Fetoprotein That Prevents Breast Cancer

Jacobson

Andersen

Bennett

2014

Cancer Prevention Research

View full text Add to dashboard Cite

Epidemiologic studies associate elevated maternal serum levels of a-fetoprotein (AFP) with reduced breast cancer risk for parous women. Laboratory studies demonstrate direct anti-breast cancer activity of AFP. Here, we review the development of a small cyclic peptide that is an active site analog of AFP, referred to as AFPep, which is composed exclusively of amino acids, is orally active, has no discernable toxicity, and is effective for the treatment and prevention of breast cancer in animal models. Cancer Prev Res; 7(6); 565-73. Ó2014 AACR.

show abstract

Structural basis for alpha fetoprotein‐mediated inhibition of caspase‐3 activity in hepatocellular carcinoma cells

Lin

Zhu

Wang

et al. 2017

Intl Journal of Cancer

View full text Add to dashboard Cite

Alpha-fetoprotein (AFP) is an early serum growth factor in the foetal liver development and hepatic carcinogenesis; However, the precise biological role of cytoplasmic AFP remains elusive. Although we recently demonstrated that cytoplasmic AFP might interact with caspase-3 and inhibit the signal transduction of apoptosis in human hepatocellular carcinoma (HCC) cells, the details of this interaction are not clear. To reveal the molecular relationship between AFP and caspase-3, we performed molecular docking, co-immunoprecipitation (Co-IP), laser confocal microscopy, site-directed mutagenesis and functional experiments to analyse the key amino acid residues in the binding site of caspase-3. The results of Co-IP, laser confocal microscopy and functional analyses were consistent with the computational model. We also used the model to explain why AFP cannot bind to caspase-8. These results provide the molecular basis for the AFP-mediated inhibition of caspase-3 activity in HCC cells. Altogether, we found that AFP interacts with caspase-3 through precise amino acids, namely loop-4 residues Glu-248, Asp-253 and His-257. The results further demonstrated that AFP plays a critical role in the inhibition of the apoptotic signal transduction that mediated by caspase-3. Thus, AFP might represent a novel biotarget for the therapy of HCC patients.

show abstract

The recombinant third domain of human alpha-fetoprotein retains the antiestrotrophic activity found in the full-length molecule

Cited by 23 publications

References 18 publications

Design and synthesis of biologically active peptides: A ‘tail’ of amino acids can modulate activity of synthetic cyclic peptides

Design and synthesis of biologically active peptides: A ‘tail’ of amino acids can modulate activity of synthetic cyclic peptides

Development of an Active Site Peptide Analog of α-Fetoprotein That Prevents Breast Cancer

Structural basis for alpha fetoprotein‐mediated inhibition of caspase‐3 activity in hepatocellular carcinoma cells

Contact Info

Product

Resources

About