scholarly journals Selective Agonists and Antagonists of Formylpeptide Receptors: Duplex Flow Cytometry and Mixture-Based Positional Scanning Libraries

2013 ◽  
Vol 84 (3) ◽  
pp. 314-324 ◽  
Author(s):  
Clemencia Pinilla ◽  
Bruce S. Edwards ◽  
Jon R. Appel ◽  
Tina Yates-Gibbins ◽  
Marc A. Giulianotti ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Positional Scanning ◽  
Selective Agonists ◽  
Positional Scanning Libraries

scholarly journals Human and mouse granzyme M display divergent and species-specific substrate specificities

2011 ◽  
Vol 437 (3) ◽  
pp. 431-442 ◽  
Author(s):  
Stefanie A.H. de Poot ◽  
Marijn Westgeest ◽  
Daniel R. Hostetter ◽  
Petra van Damme ◽  
Kim Plasman ◽  
...  
Keyword(s):  
Substrate Specificity ◽  
Specific Substrate ◽  
Structural Determinants ◽  
Cytotoxic Lymphocyte ◽  
Potent Inducer ◽  
Methionine Residue ◽  
Positional Scanning ◽  
Methionine Residues ◽  
Species Specific ◽  
Positional Scanning Libraries

Cytotoxic lymphocyte protease GrM (granzyme M) is a potent inducer of tumour cell death and a key regulator of inflammation. Although hGrM (human GrM) and mGrM (mouse GrM) display extensive sequence homology, the substrate specificity of mGrM remains unknown. In the present study, we show that hGrM and mGrM have diverged during evolution. Positional scanning libraries of tetrapeptide substrates revealed that mGrM is preferred to cleave after a methionine residue, whereas hGrM clearly favours a leucine residue at the P1 position. The kinetic optimal non-prime subsites of both granzymes were also distinct. Gel-based and complementary positional proteomics showed that hGrM and mGrM have a partially overlapping set of natural substrates and a diverged prime and non-prime consensus cleavage motif with leucine and methionine residues being major P1 determinants. Consistent with positional scanning libraries of tetrapeptide substrates, P1 methionine was more frequently used by mGrM as compared with hGrM. Both hGrM and mGrM cleaved α-tubulin with similar kinetics. Strikingly, neither hGrM nor mGrM hydrolysed mouse NPM (nucleophosmin), whereas human NPM was hydrolysed efficiently by GrM from both species. Replacement of the putative P1′–P2′ residues in mouse NPM with the corresponding residues of human NPM restored cleavage of mouse NPM by both granzymes. This further demonstrates the importance of prime sites as structural determinants for GrM substrate specificity. GrM from both species efficiently triggered apoptosis in human but not in mouse tumour cells. These results indicate that hGrM and mGrM not only exhibit divergent specificities but also trigger species-specific functions.

Identification of Novel Ligands for Vasopressin V2 Receptor from Positional Scanning Libraries

2001 ◽  
pp. 921-922
Author(s):  
Colette T. Dooley ◽  
Aric Mabini ◽  
Tyler Sylvester ◽  
Jon R. Appel ◽  
Richard A. Houghten
Keyword(s):  
Vasopressin V2 Receptor ◽  
Positional Scanning ◽  
V2 Receptor ◽  
Positional Scanning Libraries

Assessment of solution-phase positional scanning libraries based on distamycin A for the discovery of new DNA binding agents

2000 ◽  
Vol 8 (8) ◽  
pp. 2049-2057 ◽  
Author(s):  
Dale L. Boger ◽  
Michael A. Dechantsreiter ◽  
Takahiro Ishii ◽  
Brian E. Fink ◽  
Michael P. Hedrick
Keyword(s):  
Dna Binding ◽  
Solution Phase ◽  
Distamycin A ◽  
Positional Scanning ◽  
Binding Agents ◽  
Dna Binding Agents ◽  
Positional Scanning Libraries

scholarly journals A Novel Method for the Determination of Isokinetic Ratios and Its Application in the Synthesis of Two New Positional Scanning Libraries

2012 ◽  
Vol 14 (9) ◽  
pp. 503-512 ◽  
Author(s):  
Marc A. Giulianotti ◽  
Ginamarie Debevec ◽  
Radleigh G. Santos ◽  
Laura E. Maida ◽  
Wenteng Chen ◽  
...  
Keyword(s):  
Positional Scanning ◽  
Novel Method ◽  
Positional Scanning Libraries

Synthesis of positional-scanning libraries of fluorogenic peptide substrates to define the extended substrate specificity of plasmin and thrombin

10.1038/72642 ◽  
2000 ◽  
Vol 18 (2) ◽  
pp. 187-193 ◽  
Author(s):  
Bradley J. Backes ◽  
Jennifer L. Harris ◽  
Francesco Leonetti ◽  
Charles S. Craik ◽  
Jonathan A. Ellman
Keyword(s):  
Substrate Specificity ◽  
Peptide Substrates ◽  
Positional Scanning ◽  
Fluorogenic Peptide ◽  
Positional Scanning Libraries
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