The present invention relates to multimers of polypeptides which are covalently bound to molecular scaffolds such that two or more peptide loops are subtended between attachment points to the scaffold. The invention also describes the multimerization of polypeptides through various chemical linkers and hinges of various lengths and rigidity using different sites of attachments within polypeptides. In particular, the invention describes multimers of peptides which are high affinity binders and activators of CD137. The invention also includes drug conjugates comprising said peptides, conjugated to one or more effector and/or functional groups, to pharmaceutical compositions comprising said peptide ligands and drug conjugates and to the use of said peptide ligands and drug conjugates in preventing, suppressing or treating a disease or disorder mediated by CD137.

The invention provides novel peptides (e.g., linkers) and polypeptide compositions comprising the linkers (e.g., fusion proteins) and methods of using the polypeptide compositions. Peptides (e.g., linkers) are useful as tags and for engineering fusion proteins (e.g., antigen binding molecules, scFv). Polypeptide linkers described herein facilitate flexibility of linked peptides allowing for proper folding, conformation and reduced immunogenicity.

The invention provides novel peptides (e.g., linkers) and polypeptide compositions comprising the linkers (e.g., fusion proteins) and methods of using the polypeptide compositions. Peptides (e.g., linkers) are useful as tags and for engineering fusion proteins (e.g., antigen binding molecules, scFv). Polypeptide linkers described herein facilitate flexibility of linked peptides allowing for proper folding, conformation and reduced immunogenicity.

The present invention relates to the identification of peptides, and the corresponding proteins, that can be used in methods for the detection of autologous blood doping. More specifically, the invention relates to methods comprising tryptic digestion of samples of isolated red blood cell (RBC), specifically isolated RBC cytosol, followed by peptide mapping using liquid chromatography tandem-mass spectroscopy (LC-MS/MS). The methods according to the invention which enable detection of increased levels of certain peptides in samples from subjects that have been subjected to autologous blood doping, compared to samples from non-doped control subjects.

The present disclosure generally relates to genetic engineering of bacteria. More particularly, the present disclosure describes genetic engineering of E. coli to create mutant O-antigen ligase, as well as novel lipopolysaccharide molecules resulting from that genetic engineering. Methods for using those novel molecules are also described.

The present disclosure generally relates to genetic engineering of bacteria. More particularly, the present disclosure describes genetic engineering of E. coli to create mutant O-antigen ligase, as well as novel lipopolysaccharide molecules resulting from that genetic engineering. Methods for using those novel molecules are also described.

A peptide comprising the sequence shown below is added as a peptide tag to a useful protein, followed by allowing its expression.
X.sub.m(PY.sub.n).sub.qPZ.sub.r In this formula, X, Y, and Z each represent an amino acid residue independently selected from the group consisting of R, G, S, K, T, L, N, Q, and H, with the proviso that at least one Y represents K, L, N, Q, H, or R. m represents an integer of 0 to 5; n represents 1, 2, or 3; q represents an integer of 1 to 10; and r represents an integer of 0 to 10.

A peptide comprising the sequence shown below is added as a peptide tag to a useful protein, followed by allowing its expression.
X.sub.m(PY.sub.n).sub.qPZ.sub.r In this formula, X, Y, and Z each represent an amino acid residue independently selected from the group consisting of R, G, S, K, T, L, N, Q, and H, with the proviso that at least one Y represents K, L, N, Q, H, or R. m represents an integer of 0 to 5; n represents 1, 2, or 3; q represents an integer of 1 to 10; and r represents an integer of 0 to 10.

The present invention provides compounds that can modulate opioid receptors. Some compounds of the invention are modulators of - and/or -opioid receptors. Still other compounds of the invention are opioid receptor antagonists. Some compounds of the invention can modulate opioid receptors with a significantly less likelihood of developing addiction or abuse compared to conventional opioid ligands, such as morphine. In particular, compounds of the invention are of the formula: ##STR00001##
wherein Ar.sup.1 is H, optionally substituted aryl or optionally substituted heteroaryl; R.sup.1 is a heteroalkyl; R.sup.2 is alkyl; R.sup.3 is an oligopeptide or a moiety of the formula R.sup.4Y; R.sup.4 is alkylene; Y is optionally substituted heteroaryl, optionally substituted aryl or a moiety of the formula C(X.sup.2)X.sup.3R.sup.5; each of X.sup.1, X.sup.2 and X.sup.3 is independently O, NR.sup.6 or S; and each of R.sup.5 and R.sup.6 is independently H or alkyl.

The present invention provides compounds that can modulate opioid receptors. Some compounds of the invention are modulators of - and/or -opioid receptors. Still other compounds of the invention are opioid receptor antagonists. Some compounds of the invention can modulate opioid receptors with a significantly less likelihood of developing addiction or abuse compared to conventional opioid ligands, such as morphine. In particular, compounds of the invention are of the formula: ##STR00001##
wherein Ar.sup.1 is H, optionally substituted aryl or optionally substituted heteroaryl; R.sup.1 is a heteroalkyl; R.sup.2 is alkyl; R.sup.3 is an oligopeptide or a moiety of the formula R.sup.4Y; R.sup.4 is alkylene; Y is optionally substituted heteroaryl, optionally substituted aryl or a moiety of the formula C(X.sup.2)X.sup.3R.sup.5; each of X.sup.1, X.sup.2 and X.sup.3 is independently O, NR.sup.6 or S; and each of R.sup.5 and R.sup.6 is independently H or alkyl.