The mathematics of a successful deconvolution: A quantitative assessment of mixture-based combinatorial libraries screened against two formylpeptide receptors

Molecules

Volumn 18, Issue 6, 2013, Pages 6408-6424

  Santos, Radleigh G ^a   Appel, Jon R ^a   Giulianotti, Marc A ^a   Edwards, Bruce S ^b   Sklar, Larry A ^b   Houghten, Richard A ^a   Pinilla, Clemencia ^a  

^a TORREY PINES INSTITUTE FOR MOLECULAR STUDIES   (United States)

^b UNIVERSITY OF NEW MEXICO SCHOOL OF MEDICINE   (United States)

Author keywords

Combinatorial libraries; Formylpeptide receptors; Harmonic mean mixture model; Mathematical modeling; Mixture based libraries

Indexed keywords

FORMYLPEPTIDE RECEPTOR; LIGAND; PEPTIDE; PEPTIDE LIBRARY;

ARTICLE; CHEMISTRY; DRUG ANTAGONISM; HIGH THROUGHPUT SCREENING; IC 50; METHODOLOGY; PEPTIDE LIBRARY; THEORETICAL MODEL; ANTAGONISTS AND INHIBITORS; IC50; PROCEDURES;

HIGH-THROUGHPUT SCREENING ASSAYS; INHIBITORY CONCENTRATION 50; LIGANDS; MODELS, THEORETICAL; PEPTIDE LIBRARY; PEPTIDES; RECEPTORS, FORMYL PEPTIDE;

EID: 84879628757     PISSN: None     EISSN: 14203049     Source Type: Journal    
DOI: 10.3390/molecules18066408     Document Type: Article

References (15)

1. Houghten, R.A.; Pinilla, C.; Appel, J.R.; Blondelle, S.E.; Dooley, C.T.; Eichler, J.; Nefzi, A.; Ostresh, J.M. Mixture-based synthetic combinatorial libraries. J. Med. Chem. 1999, 42, 3743-3778.
2. Pinilla, C.; Appel, J.R.; Borras, E.; Houghten, R.A. Advances in the use of synthetic combinatorial chemistry: Mixture-based libraries. Nat. Med. 2003, 9, 118-122.
3. Houghten, R.A.; Pinilla, C.; Giulianotti, M.A.; Appel, J.R.; Dooley, C.T.; Nefzi, A.; Ostresh, J.M.; Yu, Y.; Maggiora, G.M.; Medina-Franco, J.L.; et al. Strategies for the use of mixture-based synthetic combinatorial libraries: Scaffold ranking, Direct testing in vivo, and enhanced deconvolution by computational methods. J. Comb. Chem. 2008, 10, 3-19.
4. Pinilla, C.; Appel, J.R.; Blanc, P.; Houghten, R.A. Rapid identification of high affinity peptide ligands using positional scanning synthetic peptide combinatorial libraries. Biotechniques 1992, 13, 901-905.
5. Dooley, C.T.; Houghten, R.A. The use of positional scanning synthetic peptide combinatorial libraries for the rapid determination of opioid receptor ligands. Life Sci. 1993, 52, 1509-1517.
6. Santos, R.G.; Giulianotti, M.A.; Dooley, C.T.; Pinilla, C.; Appel, J.R.; Houghten, R.A. Use and implications of the harmonic mean model on mixtures for basic research and drug discovery. ACS Comb. Sci. 2011, 13, 337-344.
7. Giulianotti, M.A.; Debevec, G.; Santos, R.G.; Maida, L.E.; Chen, W.; Ou, L.; Yu, Y.; Dooley, C.T.; Houghten, R.A. A novel method for the determination of isokinetic ratios and its application in the synthesis of two new positional scanning libraries. ACS Comb. Sci. 2012, 14, 503-512.
8. Ranjit, D.K.; Rideout, M.C.; Nefzi, A.; Ostresh, J.M.; Pinilla, C.; Segall, A.M. Small molecule functional analogs of peptides that inhibit lambda site-specific recombination and bind Holliday junctions. Bioorg. Med. Chem. Lett. 2010, 20, 4531-4534.
9. Rideout, M.C.; Boldt, J.L.; Vahi-Ferguson, G.; Salamon, P.; Nefzi, A.; Ostresh, J.M.; Giulianotti, M.; Pinilla, C.; Segall, A.M. Potent antimicrobial small molecules screened as inhibitors of tyrosine recombinases and Holliday junction-resolving enzymes. Mol. Divers. 2011, 15, 989-1005.
10. Reilley, K.J.; Giulianotti, M.; Dooley, C.T.; Nefzi, A.; McLaughlin, J.P.; Houghten, R.A. Identification of two novel, potent, low-liability antinociceptive compounds from the direct in vivo screening of a large mixture-based combinatorial library. AAPS J. 2010, 12, 318-329.
11. Minond, D.; Cudic, M.; Bionda, N.; Giulianotti, M.; Maida, L.; Houghten, R.A.; Fields, G.B. Discovery of novel inhibitors of a disintegrin and metalloprotease 17 (ADAM17) using glycosylated and non-glycosylated substrates. J. Biol. Chem. 2012, 287, 36473-36487.
12. Zhou, Y.; Bian, X.; Le, Y.; Gong, W.; Hu, J.; Zhang, X.; Wang, L.; Iribarren, P.; Salcedo, R.; Howard, O.M.; et al. Formylpeptide receptor FPR and the rapid growth of malignant human gliomas. J. Natl. Cancer. Inst. 2005, 97, 823-835.
13. Le, Y.; Yazawa, H.; Gong, W.; Yu, Z.; Ferrans, V.J.; Murphy, P.M.; Wang, J.M. The neurotoxic prion peptide fragment PrP(106-126) is a chemotactic agonist for the G protein-coupled receptor formyl peptide receptor-like 1. J. Immunol. 2001, 166, 1448-1451.
14. Pinilla, C.; Edwards, B.S.; Appel, J.R.; Yates-Gibbins, T.; Giulianotti, M.; Medina-Franco, J.L.; Young, S.M.; Santos, R.G.; Sklar, L.A.; Houghten, R.A. Selective agonist and antagonist of formylpeptide receptors:duplex flow cytometry and mixture-based positional scanning libraries. Mol. Pharmacol. 2013, submitted.
15. Medina-Franco, J.L.; Pinilla, C.; Appel, J.R.; Giulianotti, M.; Santos, R.G.; Yongye, A.B.; Edwards, B.S.; Sklar, L.A.; Houghten, R.A. Scanning structure-activity relantionships in combiatorial data sets: Rapid identification of activity-switches. J. Chem. Inf. Model. 2013, accepted.