The rapid identification of HIV protease inhibitors through the synthesis and screening of defined peptide mixtures

Owens, Rebecca A.; Gesellchen, Paul D.; Houchins, B.J.; DiMarchi, Richard D.

doi:10.1016/s0006-291x(05)81433-0

Cited by 99 publications

(30 citation statements)

References 15 publications

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“…10 This method has been adopted for various purposes, including the identification of human immunodeficiency virus protease inhibitors, interleukin-8-specific antagonists, inhibitor for nuclear factor of activated T cells, and ligands for opioid receptors. [11][12][13][14] Also, we already identified one bioactive hexapeptide that stimulates phosphoinositide hydrolysis by screening hexapeptide combinatorial libraries. 15 In this study we adopted the PS-SPCL method to find novel peptides that can stimulate superoxide generation in human monocytes.…”

Section: Introductionmentioning

confidence: 99%

Identification of novel chemoattractant peptides for human leukocytes

Bae

Kim

et al. 2001

Blood

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Section: Introductionmentioning

confidence: 99%

Identification of novel chemoattractant peptides for human leukocytes

Bae

Kim

et al. 2001

Blood

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“…Phage display is a powerful method for selection of novel ligands for various target proteins including enzymes [13], antibodies [14] and receptors [15,16]. Phage display libraries offer a way to identify specific ligands possessing binding specificities different from those displayed by antibodies.…”

mentioning

confidence: 99%

Identification of novel prostate‐specific antigen‐binding peptides modulating its enzyme activity

Leinonen

Koivunen³

et al. 2000

European Journal of Biochemistry

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Prostate-specific antigen (PSA) is a serine protease with highly prostate-specific expression. Measurement of PSA in serum is widely used for diagnosis and monitoring of prostate cancer. PSA dissolves the seminal gel forming after ejaculation. It has been suggested to mediate invasion and metastasis of prostate cancer but also to exert antiangiogenic activity. We have identified peptides specific for PSA by screening cyclic phage display peptide libraries. PSA-binding peptides were isolated from four different libraries and produced as a fusion protein with glutathione S-transferase (GST). The phage and fusion proteins were shown to bind to PSA specifically as indicated by lack of binding to other serine proteinases. A peptide with four cysteines showed the highest affinity for PSA. Zn 21 , an inhibitor of PSA activity, increased the affinity of the peptides to PSA. The binding specificity was characterized by cross-inhibition using monoclonal anti-PSA antibodies of known epitope specificities. The peptides bound to the same region as mAbs specific for free PSA indicating that they bind close to the active site of the enzyme. The peptides enhanced the enzyme activity of PSA against a chromogenic substrate. These results show that peptides binding to PSA and modulating its enzyme activity can be developed by phage display technique. The peptides have the potential to be used for identification of PSA variants and for imaging and targeting of prostatic tumors.

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“…For the peptide library, three degenerate positions were prepared on a RAMPS apparatus according to the 'divide-couple-recombine' strategy [22]. At each degenerate position, 0.4 mmol of peptide-resin was divided into 20 parts by weight and each part underwent double coupling with a 6-fold excess of activated hydroxybenzotriazole (HOBt) ester of a unique amino acid.…”

Section: Peptide Synthesismentioning

confidence: 99%

Amino‐terminal sequence determinants for substrate recognition by platelet‐derived growth factor receptor tyrosine kinase

Chan

Keller²,

Connors

et al. 1996

FEBS Letters

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The specificity of protein kinases has been shown to be influenced by residues near the phosphoaccepting amino acid. To examine the determinants for platelet-derived growth factor receptor (PDGFR) tyrosine kinase specificity, a peptide library with three degenerate positions N-terminal to tyrosine was constructed. After reaction with PDGFR, the most abundant phosphopeptides were isolated by immunoaffinity chromatography on a column containing monoclonal anti-phosphotyrosine antibody. Further separation of bound phosphopeptides with reverse-phase HPLC led to the identification of three optimal substrates for PDGFR: Ala-Ala-Asn-Ile-Thr-Tyr-Ala-Ala-ArgArg-Gly, Ala-Ala-Asn-Arg-Thr-Tyr-Ala-Ala-Arg-Arg-Gly and Ala-Ala-Leu-Ile-Thr-Tyr-Ala-Ala-Arg-Arg-Gly, where underlined residues are in the degenerate positions of the peptide library. Kinetic analyses of the three individual peptides (synthesized separately) showed these peptides to be among the best reported substrates for PDGFR. Our results expand the range of amino acid residues that have been shown to serve as recognition elements for receptor tyrosine kinases.

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The rapid identification of HIV protease inhibitors through the synthesis and screening of defined peptide mixtures

Cited by 99 publications

References 15 publications

Identification of novel chemoattractant peptides for human leukocytes

Identification of novel chemoattractant peptides for human leukocytes

Identification of novel prostate‐specific antigen‐binding peptides modulating its enzyme activity

Amino‐terminal sequence determinants for substrate recognition by platelet‐derived growth factor receptor tyrosine kinase

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