Efficient assembly of peptomers on continuous surfaces

Tetrahedron Letters

Volumn 40, Issue 23, 1999, Pages 4317-4318

  Thomas, Ast ^a   Heine, Niklas ^a   Germeroth, Lothar ^b   Schneider Mergener, Jens ^a,c   Wenschuh, Holger ^c  

^a CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^b ChemotopiX GmbH   (Germany)

^c Jerini Bio Tools GmbH   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

CELLULOSE; PEPTIDE DERIVATIVE; PEPTOMER; UNCLASSIFIED DRUG;

ACYLATION; ARTICLE; ESTERIFICATION; PEPTIDE SYNTHESIS; SOLID PHASE EXTRACTION; SOLUBILITY; STEREOSPECIFICITY; SURFACE PROPERTY; SYNTHESIS; ULTRAVIOLET IRRADIATION;

EID: 0033522834     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(99)00775-3     Document Type: Article

References (11)

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2. U. Reineke, A. Kramer, J. Schneider-Mergener, Curr. Top. Microbiol. Immunol. 1999, in press.
3. N. Heveker, M. Montes, L. Germeroth, A. Amara, A. Trautmann, M. Alizon, J. Schneider-Mergener, Curr. Biol. 1998, 8, 369.
4. 2) can be achieved with increased reaction times, use of neat 4,7,10-trioxa-1,13-tridecanediamine or increased temperature (80°C). In contrast to an earlier report (R. Volkmer-Engert et al., Tetrahedron Lett. 1997, 8, 1029) the present method yields in higher and adjustable loadings at markedly shorter reaction times.
5. C. Holmes, D. G. Jones, J. Org. Chem. 1995, 60, 2318.
6. TBTU, PyBOP and HATU (4-8 eq. relative to the amino-loading) were used for linker attachment. Preactivation was performed for 5 min with DIEA or NMI (1.0 or 2.0 eq.). DIC was used with 1.0 eq. NMI or without base. In all cases double couplings (2×15 min) were applied. Dimmed light is recommended due to the light sensitivity of the linker system.
7. R. N. Zuckermann, J. M. Kerr, S. B. H. Kent, W. H. Moos, J. Am. Chem. Soc. 1992, 114, 10646.
8. Spot steps were performed three times (reaction time: 15 min each).
9. S. Østergaard, A. Holm, Mol Div. 1997, 3, 17.
10. Fmoc amino acids: E(OtBu), F, G, I, K(Boc), M, P, Q(Trt), S(tBu), V, Y(tBu); activations: HATU, TBTU, PyAOP, PyBOP, PyBroP (1.0 eq., used with 1.0 eq. DIEA to suppress esterification), DIC/HOAt, DIC, fluorides. In contrast to earlier results (H. Wenschuh et al., J. Org. Chem. 1994, 59, 3275) on coupling of sterically hindered α,α-dialkylated amino acids, anhydrides were more efficient (yield: 90-100%; Q(Trt): 65%) than fluorides (yield: 70-90%; Q(Trt): 30%) for the acylation of secondary amines.
11. H. I. Chen, A. Einbond, S. J. Kwak, H. Linn, E. Koepf, S. Peterson, J. W. Kelly, M. Sudol, J. Biol. Chem. 1997, 27, 17070. L. A. Carpino is thanked for critical reading of the manuscript and A. Rosenberg for skillful technical assistance.