PERETEZ, DAVID,CONNOLLY, MICHAEL D,ZUCKERMANN, RONALD,GAO, MAN,SHIMIZU, ROBERT M,TIMOTEO, GULLIVER
申请号：
NZ59484406
公开号：
NZ594844A
申请日:
2006.09.08
申请国别(地区):
NZ
年份:
2013
代理人:
摘要：
Disclosed is a method of producing a peptoid reagent capable of preferentially interacting with a pathogenic form of a conformational disease protein as compared to a non-pathogenic form of the conformational disease protein. The method comprises synthesizing a peptoid comprising amino acids of a prion protein fragment comprising the sequence KKRKP (SEQ ID NO: 12) or QWNKPSKPKT (residues 4-12 of SEQ ID NO: 75), wherein the residues of said sequence are each substituted for N-substituted glycine residues selected from the group consisting of (S)-N-(1-phenylethyl)glycine (Nspe), N-(2-methoxyethyl)glycine (Nme), N-(4-guanidinobutyl) glycine (Ngb), N-(2-3-indolylethyl)glycine (Ntrp), N-(4-aminobutyl)glycine (Nab), N-benzylglycine (Nbn), N-(2-(4-methoxyphenyl)ethyl)glycine (Nmpe), N-(2-hydroxyethyl)glycine (Nhye), and N-(4-aminoethyl)glycine (Nae), wherein the substitutions are according to the following replacement scheme: Each Lys residue of the sequence is replaced with Nab or Nspe or Nhye or Nae Each Arg residue of the sequence is replaced with Nab or Ngb or Nae Each Pro residue of the sequence is replaced with Nab or Nspe or Nbn or Nmpe Gln, Asn, Ser and Thr are each replaced with Nme and Trp is replaced with Ntrp wherein the synthesized peptoid has a formula of: Xa-(Q)n-Xb wherein: -(Q)n- defines a peptoid region comprising at least 50% N-substituted glycine residues, wherein Q defines an amino acid sequence thereof comprising said N substituted glycine residues, and n is an integer having a value from 5 to 30 defining a length of Q Xa is absent or selected from the group consisting of: H, (C1-C6)alkyl, cycloalkyl, aryl, aralkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl, (C1-C6)acyl, amino(Cl-6)acyl, an amino acid, an amino protecting group, and a polypeptide of 2 to 100 amino acids in length, and wherein Xa if present is optionally substituted by a conjugate moiety that is optionally attached through a linker moiety and Xb is absent or an amino acid that is o
