Peptide-chelator conjugates

DETAILED DESCRIPTION OF THE INVENTION The invention provides peptide-chelator conjugates that when complexed with a diagnostically useful metal are useful for imaging sites of inflammation.
The peptide-chelator conjugate, also referred to as "conjugate", incorporates an antagonist of tuftsin coupled at its N-terminus to any metal chelator, the peptide component consisting of the amino acid sequence Thr-Lys-Pro-Pro-Arg represented by the single letter coed TKPPR (Seq ID no: 2) hereinafter referred to as "the peptide".
It is understood that the peptide may be extended at its C-terminus by 1 to 3 amino acid residues or may be modified at the C-terminus for example amidated such that the targetting activity of the peptide is not substantially inhibited.
In an embodiment of the present invention, the peptide is coupled to the metal chelators (I) illustrated above which is disclosed in co-pending United States application in the name of Pollak et al, filed on 22 Dec.
1993, incorporated herein by reference and metal chelators (II).
The terms defining the variables R.
sub.
1 -R.
sub.
4 and T as used hereinabove in formula (I) and (II) have the following meanings: "alkyl" refers to a straight or branched C.
sub.
1 -C.
sub.
8 chain and includes lower C.
sub.
1 -C.
sub.
4 alkyl; "alkoxy" refers to straight or branched C.
sub.
1 -C.
sub.
8 alkoxy and includes lower C.
sub.
1 -C.
sub.
4 alkoxy; "thiol" refers to a sulfhydryl group that may be substituted with an alkyl group to form a thioether; "sulfur protecting group" refers to a chemical group that is bonded to a sulfur atom and inhibits oxidation of sulfur and includes groups that are cleaved upon chelation of the metal.
Suitable sulfur protecting groups include known alkyl, aryl, acyl, alkanoyl, aryloyl, mercaptoacyl and organothio groups.
"linking group" refers to a chemical group that serves to couple the peptide to the chelator while not adversely affecting either the targetting function of the peptide or the metal binding function of the chelator.
Suitable linking groups include alkyl chains and amino acid chains functionalized with a reactive groups for coupling to the peptide or chelator