Aspartic Acid Side-Chain Benzyl Ester as a Multifunctionalization Precursor for Synthesis of Branched and Cyclic Arginylglycylaspartic Acid PeptidesThis work was supported by the National Natural Science Foundation of China (NNSFC, No. 21372238 and 21572244) and the Personalized Medicines: Molecular Signature-Based Drug Discovery and Development Strategic Priority Research Program of the Chinese Academy of Sciences, Grant No. XDA12020311.
Received: 16 April 2017
Accepted after revision: 16 May 2017
29 June 2017 (online)
◊ These authors contributed equally to this work.
Published as part of the Cluster Recent Advances in Protein and Peptide Synthesis
Here, we report a peptide aspartic acid side-chain benzyl ester as a useful precursor that can be efficiently converted into various functional groups, including acid, amide, carbonyl hydrazide, carbonyl azide, or thio ester groups, without other protection for the peptide. With this strategy, we synthesized a series of novel branched and cyclic arginylglycylaspartic acid peptides through successive peptide C-terminal ligation and side-chain ligation based on a side-chain carbonyl azide or thio ester.
Key wordspeptide side-chain ligation - side-chain benzyl ester - peptide hydrazide - arginylglycylaspartic acid peptides - branched cyclic peptides
Notes and References
- 1 Robinson JA. J. Pept. Sci. 2013; 19: 127
- 2 Yahi N. Sabatier JM. Baghdiguian S. Gonzalez-Scarano F. Fantini J. J. Virol. 1995; 69: 320
- 3 Stigers KD. Soth MJ. Nowick JS. Curr. Opin. Chem. Biol. 1999; 3: 714
- 4 Stavrakoudis A. Makropoulou S. Tsikaris V. Sakarellos-Daitsiotis M. Sakarellos C. Demetropoulos IN. J. Pept. Sci. 2003; 9: 145
- 5 Gorse GJ. Keefer MC. Belshe RB. Matthews TJ. Forrest BD. Hsieh RH. Koff WC. Hanson CV. Dolin R. Weinhold KJ. Frey SE. Ketter N. Fast PE. J. Infect. Dis. 1996; 173: 330
- 6 Wang LX. Curr. Opin. Drug Discovery Devel. 2006; 9: 194
- 7 Sheridan JM. Hayes GM. Austen BM. J. Pept. Sci. 1999; 5: 555
- 8 Neumiller JJ. Campbell RK. Ann. Pharmacother. 2009; 43: 1433
- 9 Mendive-Tapia L. Preciado S. Garcia J. Ramón R. Kielland N. Albericio F. Lavilla R. Nat. Commun. 2015; 6: 7160
- 10 Ruoslahti E. Pierschbacher MD. Science 1987; 238: 491
- 11 Haubner R. Gratias R. Diefenbach B. Goodman SL. Jonczyk A. Kessler H. J. Am. Chem. Soc. 1996; 118: 7461
- 12 Liu Z. Wang F. Chen X. Drug Dev. Res. 2008; 69: 329
- 13 Dechantsreiter MA. Planker E. Matha B. Lohof E. Holzemann G. Jonczyk A. Goodman SL. Kessler H. J. Med. Chem. 1999; 42: 3033
- 14 Oba M. Fukushima S. Kanayama N. Aoyagi K. Nishiyama N. Koyama H. Kataoka K. Bioconjugate Chem. 2007; 18: 1415
- 15 Lu J. Tian X.-B. Huang W. Chin. Chem. Lett. 2015; 26: 946
- 16 Fang G.-M. Li Y.-M. Shen F. Huang Y.-C. Li J.-B. Lin Y. Cui H.-K. Liu L. Angew. Chem. Int. Ed. 2011; 50: 7645
- 17 Zheng J.-S. Tang S. Qi Y.-K. Wang Z.-P. Liu L. Nat. Protoc. 2013; 8: 2483
- 18 Li D. Elbert DL. J. Pept. Res. 2002; 60: 300
- 19 Bloomberg GB. Askin D. Gargaro AR. Tanner MJ. A. Tetrahedron Lett. 1993; 34: 4709
- 20 Zhou C. Li Y.-H. Jiang Z.-H. Ahn K.-D. Hu T.-J. Wang Q.-H. Wang C.-H. Chin. Chem. Lett. 2016; 27: 685
- 21 Pasunooti KK. Yang R. Vedachalam S. Gorityala BK. Liu C.-F. Liu X.-W. Bioorg. Med. Chem. Lett. 2009; 19: 6268
- 22 Side-Chain Peptide Hydrazide Synthesis and Successive Side-Chain Ligation; General Procedure The side-chain benzyl ester peptide (2 mM) was treated with 5% N2H4 in DMF at r.t. for 15–30 mins until conversion was complete (HPLC). The product was purified by preparative HPLC, and the resulting side-chain peptide hydrazide was then treated with NaNO2 (10 equiv) in a pH 2 buffer of 6.0 M guanidine hydrochloride and 0.2 M aq NaH2PO4 at –10 °C for 15 min to give the corresponding carbonyl azide. MPAA (50 equiv) was then added, the pH of the residue was adjusted to pH 5.5 with 1.0 M aq NaOH, and the mixture was kept at –10 °C for 15 min to give the side-chain thio ester. A Cys-peptide (2 equiv) or an amino-RGD peptide (5 equiv) was added then for side-chain ligation at r.t. for 4–8 h. The ligation product of the branched peptide was purified by preparative HPLC. For details and HPLC and MS data, see the Supplementary Information.
- 23 Tian X. Li J. Huang W. Tetrahedron Lett. 2016; 57: 4264