Metabolic stability of peptidomimetics: N-methyl and aza heptapeptide analogs of a PKB/Akt inhibitor

Chemical Biology and Drug Design

Volumn 78, Issue 5, 2011, Pages 887-892

  Tal Gan, Yftah ^a   Freeman, Noam S ^a   Klein, Shoshana ^a   Levitzki, Alexander ^a   Gilon, Chaim ^a  

^a HEBREW UNIVERSITY OF JERUSALEM   (Israel)

Author keywords

Aza peptide; Chymotrypsin; N methylation; Peptidomimetics; PKB Akt; Trypsin

Indexed keywords

AZA PEPTIDE; CHYMOTRYPSIN; N METHYLATED PEPTIDE; PEPTIDE; PEPTIDOMIMETIC AGENT; PROTEIN KINASE B INHIBITOR; PTR 6154; TRYPSIN; UNCLASSIFIED DRUG;

ARTICLE; ENZYMATIC DEGRADATION; METABOLIC STABILITY; METHYLATION; PRIORITY JOURNAL; PROTEIN MODIFICATION; PROTEIN STABILITY;

AMINO ACID SEQUENCE; AZA COMPOUNDS; CHYMOTRYPSIN; OLIGOPEPTIDES; PEPTIDOMIMETICS; PROTEIN KINASE INHIBITORS; PROTEIN-SERINE-THREONINE KINASES; PROTO-ONCOGENE PROTEINS C-AKT; TRYPSIN;

EID: 80054092007     PISSN: 17470277     EISSN: 17470285     Source Type: Journal    
DOI: 10.1111/j.1747-0285.2011.01207.x     Document Type: Article

References (54)

1. Ahn J.M., Boyle N.A., MacDonald M.T., Janda K.D. (2002) Peptidomimetics and peptide backbone modifications. Mini Rev Med Chem;2:463-473.
2. Gante J. (1994) Peptidomimetics - tailored enzyme-inhibitors. Angew Chem Int Edit;33:1699-1720.
3. Naider F., Goodman M. (2002) Historical Aspects. In: Synthesis of Peptides and Peptidomimetics. Goodman M., Toniolo C., Moroder L., Felix A., editors. Stuttgart-New York: Thieme; p. 1-16.
4. Adessi C., Soto C. (2002) Converting a peptide into a drug: strategies to improve stability and bioavailability. Curr Med Chem;9:963-978.
5. Cody W.L., He J.X., Reily M.D., Haleen S.J., Walker D.M., Reyner E.L., Stewart B.H., Doherty A.M. (1997) Design of a potent combined pseudopeptide endothelin-A/endothelin-B receptor antagonist, Ac-DBhg16-Leu-Asp-Ile-[NMe]Ile-Trp21 (PD 156252): examination of its pharmacokinetic and spectral properties. J Med Chem;40:2228-2240.
6. Mazur R.H., James P.A., Tyner D.A., Hallinan E.A., Sanner J.H., Schulze R. (1980) Bradykinin analogs containing Nalpha-methyl amino-acids. J Med Chem;23:758-763.
7. Gilon C., Dechantsreiter M.A., Burkhart A., Friedler A., Kessler H. (2003) Synthesis of Peptides and Peptidomimetics. In: Goodman M., Felix A., Moroder L., Toniolo C., editors. Synthesis of Peptides and Peptidomimetics. Stuttgart, New York: Thieme; p. 215.
8. Chatterjee J., Gilon C., Hoffman A., Kessler H. (2008) N-methylation of peptides: a new perspective in medicinal chemistry. Acc Chem Res;41:1331-1342.
9. Ovadia O., Greenberg S., Laufer B., Gilon C., Hoffman A., Kessler H. (2010) Improvement of drug-like properties of peptides: the somatostatin paradigm. Expert Opin Drug Discov;5:655-671.
10. Biron E., Chatterjee J., Ovadia O., Langenegger D., Brueggen J., Hoyer D., Schmid H.A., Jelinek R., Gilon C., Hoffman A., Kessler H. (2008) Improving oral bioavailability of peptides by multiple N-methylation: somatostatin analogues. Angew Chem Int Ed Engl;47:2595-2599.
11. Haviv F., Fitzpatrick T.D., Swenson R.E., Nichols C.J., Mort N.A., Bush E.N., Diaz G., Bammert G., Nguyen A., Rhutasel N.S., Nellans H.N., Hoffman D.J., Johnson E.S., Greer J. (1993) Effect of N-methyl substitution of the peptide-bonds in luteinizing-hormone-releasing hormone agonists. J Med Chem;36:363-369.
12. Fiacco S.V., Roberts R.W. (2008) N-methyl scanning mutagenesis generates protease-resistant G protein ligands with improved affinity and selectivity. Chembiochem;9:2200-2203.
13. Goodfellow V.S., Marathe M.V., Kuhlman K.G., Fitzpatrick T.D., Cuadrado D., Hanson W., Zuzack J.S., Ross S.E., Wieczorek M., Burkard M., Whalley E.T. (1996) Bradykinin receptor antagonists containing N-substituted amino acids: in vitro and in vivo B(2) and B(1) receptor antagonist activity. J Med Chem;39:1472-1484.
14. Tonelli A. (1976) The effects of isolated N-methylated residues on the conformational characteristics of polypeptides. Biopolymers;15:1615-1622.
15. Ron D., Gilon C., Hanani M., Vromen A., Selinger Z., Chorev M. (1992) N-methylated analogs of Ac[Nle28, 31]CCK(26-33): synthesis, activity, and receptor selectivity. J Med Chem;35:2806-2811.
16. Dechantsreiter M.A., Planker E., Matha B., Lohof E., Holzemann G., Jonczyk A., Goodman S.L., Kessler H. (1999) N-methylated cyclic RGD peptides as highly active and selective alpha(V)beta(3) integrin antagonists. J Med Chem;42:3033-3040.
17. Laufer R., Wormser U., Friedman Z.Y., Gilon C., Chorev M., Selinger Z. (1985) Neurokinin B is a preferred agonist for a neuronal substance P receptor and its action is antagonized by enkephalin. Proc Natl Acad Sci U S A;82:7444-7448.
18. Wormser U., Laufer R., Hart Y., Chorev M., Gilon C., Selinger Z. (1986) Highly selective agonists for substance-P receptor subtypes. EMBO J;5:2805-2808.
19. Weltrowska G., Berezowska I., Lemieux C., Chung N.N., Wilkes B.C., Schiller P.W. (2009) N-methylated cyclic enkephalin analogues retain high opioid receptor binding affinity. Chem Biol Drug Des;75:182-188.
20. Rovero P., Pestellini V., Patacchini R., Santicioli P., Maggi C.A., Meli A. (1989) Conformationally constrained tachykinins: N-methylated analogues of neurokinin A. Biopolymers;28:65-67.
21. Chatterjee J., Ovadia O., Zahn G., Marinelli L., Hoffman A., Gilon C., Kessler H. (2007) Multiple N-methylation by a designed approach enhances receptor selectivity. J Med Chem;50:5878-5881.
22. Bach A.C., Eyermann C.J., Gross J.D., Bower M.J., Harlow R.L., Weber P.C., DeGrado W.F. (1994) Structural studies of a family of high-affinity ligands for GPIIb/IIIa. J Am Chem Soc;116:3207-3219.
23. Smith J.A., Pease L.G. (1980) Reverse turns in peptides and proteins. CRC Crit Rev Biochem;8:315-399.
24. Sagan S., Karoyan P., Lequin O., Chassaing Gr., Lavielle S. (2004) N- and C-alpha-methylation in biologically active peptides: synthesis, structural and functional aspects. Curr Med Chem;11:2799-2822.
25. Biron E., Kessler H. (2005) Convenient synthesis of N-methylamino acids compatible with Fmoc solid-phase peptide synthesis. J Org Chem;70:5183-5189.
26. Biron E., Chatterjee J., Kessler H. (2006) Optimized selective N-methylation of peptides on solid support. J Pept Sci;12:213-219.
27. Teixido M., Albericio F., Giralt E. (2005) Solid-phase synthesis and characterization of N-methyl-rich peptides. J Pept Res;65:153-166.
28. White K.N., Konopelski J.P. (2005) Facile synthesis of highly functionalized N-methyl amino acid esters without side-chain protection. Org Lett;7:4111-4112.
29. Di Gioia M.L., Leggio A., Liguori A., Perri F. (2007) Solid-phase synthesis of N-nosyl- and N-Fmoc-N-methyl-alpha-amino acids. J Org Chem;72:3723-3728.
30. Di Gioia M.L., Leggio A., Liguori A., Perri F., Siciliano C., Viscomi M.C. (2010) A preparation of N-Fmoc-N-methyl-alpha-amino acids and N-nosyl-N-methyl-alpha-amino acids. Amino Acids;38:133-143.
31. Leggio A., Belsito E.L., De Marco R., Liguori A., Perri F., Viscomi M.C. (2010) An efficient preparation of N-methyl-alpha-amino acids from N-nosyl-alpha-amino acid phenacyl esters. J Org Chem;75:1386-1392.
32. Nestor J.J. Jr (2009) The medicinal chemistry of peptides. Curr Med Chem;16:4399-4418.
33. Gentilucci L., Tolomelli A., Squassabia F. (2006) Peptides and peptidomimetics in medicine, surgery and biotechnology. Curr Med Chem;13:2449-2466.
34. Steffansen B., Nielsen C.U., Frokjaer S. (2005) Delivery aspects of small peptides and substrates for peptide transporters. Eur J Pharm Biopharm;60:241-245.
35. Harris K.S., Casey J.L., Coley A.M., Karas J.A., Sabo J.K., Tan Y.Y., Dolezal O., Norton R.S., Hughes A.B., Scanlon D., Foley M. (2009) Rapid optimization of a peptide inhibitor of malaria parasite invasion by comprehensive N-methyl scanning. J Biol Chem;284:9361-9371.
36. Rajeswaran W.G., Hocart S.J., Murphy W.A., Taylor J.E., Coy D.H. (2001) N-methyl scan of somatostatin octapeptide agonists produces interesting effects on receptor subtype specificity. J Med Chem;44:1416-1421.
37. Thormann M., Hofmann H.J. (1999) Conformational properties of azapeptides. Theochem-J Mol Struct;469:63-76.
38. Gante J. (1989) Azapeptides. Synthesis (Stuttg);405-413.
39. Boeglin D., Lubell W.D. (2005) Aza-amino acid scanning of secondary structure suited for solid-phase peptide synthesis with Fmoc chemistry and aza-amino acids with heteroatomic side chains. J Comb Chem;7:864-878.
40. Melendez R.E., Lubell W.D. (2004) Aza-amino acid scan for rapid identification of secondary structure based on the application of N-boc-aza-dipeptides in peptide synthesis. J Am Chem Soc;126:6759-6764.
41. Zega A., Urleb U. (2002) Azapeptides. Acta Chim Slov;49:649-662.
42. Zega A. (2005) Azapeptides as pharmacological agents. Curr Med Chem;12:589-597.
43. Gante J., Kahlenberg H. (1991) Synthesis of a novel azapeptide - renin inhibitor. Chemiker-Zeitung;115:215-217.
44. Niedrich H., Oehme C. (1972) Hydrazine compounds as hetero components in peptides. XV. Synthesis of eledoisin octapeptides with carbazyl residues azaglycine and alpha azaasparagine in place of glycine and asparagine. J Fur Prakt Chem;314:759-768.
45. Niedrich H., Oehme C., Bergmann J. (1974) Hydrazine compounds as hetero-constituents in peptides. XIX. Synthesis of eledoisine peptides which contain N2-methyl-carbazoyl radical azaalanine. J Prakt Chem;316:741-749.
46. Dutta A.S., Giles M.B. (1976) Polypeptides. Part XIV. A comparative study of the stability towards enzymes of model tripeptides containing alpha-aza-amino-acids, L-amino-acids, and D-amino-acids. J Chem Soc [Perkin 1]:244-248.
47. Ganong W.F. (1995) Review of Medical Physiology, 12th edn. Los Altos: Lange Medical Publications.
48. Rawlings N.D., Barrett A.J. (1994) [2] Families of serine peptidases. Methods Enzymol;244:19-61.
49. Pakkala M., Hekim C., Soininen P., Leinonen J., Koistinen H., Weisell J., Stenman U.H., Vepsäläinen J., Närvänen A. (2007) Activity and stability of human kallikrein-2-specific linear and cyclic peptide inhibitors. J Pept Sci;13:348-353.
50. Tal-Gan Y., Freeman N.S., Klein S., Levitzki A., Gilon C. (2010) Synthesis and structure-activity relationship studies of peptidomimetic PKB/Akt inhibitors: the significance of backbone interactions. Bioorg Med Chem;18:2976-2985.
51. Hayouka Z., Hurevich M., Levin A., Benyamini H., Iosub A., Maes M., Shalev D.E., Loyter A., Gilon C., Friedler A. (2010) Cyclic peptide inhibitors of HIV-1 integrase derived from the LEDGF/p75 protein. Bioorg Med Chem;18:8388-8395.
52. Litman P., Ohne O., Ben-Yaakov S., Shemesh-Darvish L., Yechezkel T., Salitra Y., Rubnov S., Cohen I., Senderowitz H., Kidron D., Livnah O., Levitzki A., Livnah N. (2007) A novel substrate mimetic inhibitor of PKB/Akt inhibits prostate cancer tumor growth in mice by blocking the PKB pathway. Biochemistry;46:4716-4724.
53. Hurevich M., Tal-Gan Y., Klein S., Barda Y., Levitzki A., Gilon C. (2010) Novel method for the synthesis of urea backbone cyclic peptides using new Alloc-protected glycine building units. J Pept Sci;16:178-185.
54. Freeman N.S., Tal-Gan Y., Klein S., Levitzki A., Gilon C. (2011) Microwave-assisted solid phase aza-peptide synthesis: aza-scan of a PKB/Akt inhibitor using aza-arginine and aza-proline precursors. J Org Chem;76:3078-3085.