An M13 phage library displaying random 38-amino-acid peptides as a source of novel sequences with affinity to selected targets

Kay, Brian K.; Adey, Nils B.; He, Yunsheng; Manfredi, John P.; Mataragnon, Anthea H.; Fowlkes, Dana M.

doi:10.1016/0378-1119(93)90153-t

Cited by 157 publications

(81 citation statements)

References 14 publications

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“…The construction of the phage peptide library was done as described elsewhere (15), with the difference that the library was plated without amplification. Each plaque formed was amplified in Escherichia coli DH5aFЈ (Life Technologies, Rockville, MD) as described (16), and the supernatants were tested for binding to C3.…”

Section: Construction Of the Phage-displayed Random Peptide Librarymentioning

confidence: 99%

Studies of Structure-Activity Relations of Complement Inhibitor Compstatin

Soulika

Morikis

Sarrias

et al. 2003

The Journal of Immunology

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Compstatin, a 13-mer cyclic peptide, is a novel and promising inhibitor of the activation of the complement system. In our search for a more active analog and better understanding of structure-functions relations, we designed a phage-displayed random peptide library based on previous knowledge of structure activity relations, in which seven amino acids deemed necessary for structure and activity were kept fixed while the remaining six were optimized. Screening of this library against C3 identified four binding clones. Synthetic peptides corresponding to these clones revealed one analog, called acetylated Ile1Leu/His9Trp/Thr13Gly triple replacement analog of compstatin corresponding to clone 640 (Ac-I1L/H9W/T13G), which was more active than compstatin. This newly identified peptide had 4-fold higher activity when compared with the originally isolated form of compstatin and 1.6-fold higher activity when compared with acetylated compstatin (Ac-compstatin). The structures of Ac-I1L/H9W/T13G and Ac-compstatin were studied by nuclear magnetic resonance, compared with the structure of compstatin, and found to be very similar. The binding of Ac-I1L/H9W/T13G and the equally active acetylated analog with His9Ala replacement (Ac-H9A) to C3 was evaluated by surface plasmon resonance, which suggested similarity in their binding mechanism but difference when compared with Ac-compstatin. Compensatory effects of flexibility outside the β-turn and tryptophan ring stacking may be responsible for the measured activity increase in Ac-I1L/H9W/T13G and acetylated analog with His9Ala replacement and the variability in binding mechanism compared with Ac-compstatin. These data demonstrate that tryptophan is a key amino acid for activity. Finally, the significance of the N-terminal acetylation was examined and it was found that the hydrophobic cluster at the linked termini of compstatin is essential for binding to C3 and for activity.

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Section: Construction Of the Phage-displayed Random Peptide Librarymentioning

confidence: 99%

Studies of Structure-Activity Relations of Complement Inhibitor Compstatin

Soulika

Morikis

Sarrias

et al. 2003

The Journal of Immunology

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“…Much of this work used arrays of overlapping synthetic peptides (Houghten, 1985;Appel et al, 1990;Pinilla et al, 1993) or proteolyzed fragments of the natural antigen (Ellgaard et al, 1995). Libraries of phagedisplayed peptides, some of which contained relatively short peptides (420 amino acids) (Scott and Smith, 1990;Stephen and Lane, 1992;Renschler et al, 1994;Stephen et al, 1995) and others that contained longer peptides (420 amino acids) (Kay et al, 1993;Grihalde et al, 1995;Chen et al, 1996) have been used as alternative sources of epitopes. These phage libraries were all tested against antibodies recognizing continuous or discontinuous linear epitopes.…”

Section: Introductionmentioning

confidence: 99%

Identification of an allosteric binding site on the transcription factor p53 using a phage-displayed peptide library

Ravera¹,

Cárcamo²,

Brissette³

et al. 1998

Oncogene

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“…loops 2, 3 and/or 5, see figure 4A). Among the different strategies that have been developed to produce clonable degenerated DNA sequences [26][27][28] we have used method described by Scott and Smith 29 (Fig. 5).…”

Section: Biosynthesis Of Cyclic Peptide Based Libraries In Vivomentioning

confidence: 99%

Developing New Tools for the in vivo Generation/Screening of Cyclic Peptide Libraries. A New Combinatorial Approach for the Detection of Bacterial Toxin Inhibitors

Camarero¹

2006

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An M13 phage library displaying random 38-amino-acid peptides as a source of novel sequences with affinity to selected targets

Cited by 157 publications

References 14 publications

Studies of Structure-Activity Relations of Complement Inhibitor Compstatin

Studies of Structure-Activity Relations of Complement Inhibitor Compstatin

Identification of an allosteric binding site on the transcription factor p53 using a phage-displayed peptide library

Developing New Tools for the in vivo Generation/Screening of Cyclic Peptide Libraries. A New Combinatorial Approach for the Detection of Bacterial Toxin Inhibitors

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