[54] PEPTIDE SYNTHESIS METHOD AND SOLID SUPPORT FOR USE IN THE METHOD
[75] Inventors: Rolf H. Berg, Frederiksberg;
Kristoffer Almdal, Copenhagen;
Walther B. Pedersen, Roskilde; Arne
Holm, Holte, all of Denmark; James
P. Tam, New York, N.Y.; Robert B.
Merrifield, Cresskill, N.J.
[73] Assignee: Riso National Laboratory, Roshilde, Denmark
[21] Appl. No.: 882,059
[22] Filed: May 12,1992
Related U.S. Application Data
[63] Continuation of Ser. No. 398,846, Aug. 25, 1989, abandoned, which is a continuation-in-part of Ser. No. 239,525, Sep. 1, 1988, abandoned.
[51] Int. CI.* C08F 283/00; C08G 63/48;
C08G 63/91
[52] U.S. CI 525/54.11; 530/333;
530/334
[58] Field of Search 525/54.11; 530/333,
530/334
[56] References Cited
U.S. PATENT DOCUMENTS
3,795,664 3/1974 William et al 530/334
3,951,741 4/1976 Pfaender et al 435/68.1
4,631,211 12/1986 Houghten 428/35
4,923,901 5/1990 Koester et al 521/53
FOREIGN PATENT DOCUMENTS
0065069 11/1982 European Pat. Off. .
0187391 7/1986 European Pat. Off. .
1544668 11/1968 France .
1234982 6/1971 United Kingdom .
1344706 1/1974 United Kingdom .
OTHER PUBLICATIONS
US005258454A
[ii] Patent Number: 5,258,454 [45] Date of Patent: Nov. 2,1993
Styrene to Polyethylene, Sueo Machi, Ihab Kamel and Joseph Silverman, (1970).
Garnett and Yen American Counsel Society 1980 "Acid Effects In The Radiation Grafting Of Monomers To Polymers, Particularly Polyethylene". Odian et al Journal of Applied Polymer Science vol. 7, pp. 245-250 (1963) "Accelerative Effects In Radiation-Induced Graft Polymerization". Odian et al Journal of Polymer Science, vol. XLII Issue 140 (1960) "The Accelerating Effect of Methanol on the Gamma Radiation Induced Graft Copolymerization of Styrene to Polyethylene".
Odian et al Journal of Polymer Science vol. 55, pp. 663-673 (1961) "Radiation-Induced Graft Polymerization: The Trommsdorff Effect of Methanol".
Primary Examiner—Nathan M. Nutter
Attorney, Agent, or Firm—Wyatt, Gerber, Burke and
Badie
[57] ABSTRACT
A method for the solid-phase synthesis of peptides or proteins in high yield and high purity uses a solid-support consisting of a functionalized polystyrene-grafted polymer substrate, the grafted polystyrene chains being substantially non-cross-linked and having a chain molecular weight, not including optional non-reactive substituents, of at least 200,000, preferably in the range of 600,000-1,200,000. Particularly suitable polymer substrates are substrates of a polyolefin such as polyethylene. The method is particularly well-suited to the compartmentalized synthesis of a multitude of peptides or proteins in a parallel and substantially simultaneous fashion.
Preferred embodiments of a solid support for performing the synthesis are prepared from thin polyethylene sheet or film which has been grafted with polystyrene chains in a radical-initiated process in which the polyethylene sheet or film is immersed in a solution of optionally substituted styrene monomer in an alcohol such as methanol, the volume percentage of styrene in the solution preferably being about 30% v/v, and subjected to gamma irradiation.
