Peptide pharmaceuticals for insulin resistance

A peptide product comprising a surfactant X covalently attached to a peptide, the peptide comprising a linker amino acid U and at least one other amino acid:

• wherein the surfactant X is a group of Formula I:
• wherein:
• R1a is independently at each occurrence a bond, H, a substituted or unsubstituted C1-C30 alkyl group, a substituted or unsubstituted alkoxyaryl group, a substituted or unsubstituted aralkyl group, or a steroid nucleus containing moiety;
• R1b, R1c and R1d are independently at each occurrence a bond, H, a substituted or unsubstituted C1-C30 alkyl group, a substituted or unsubstituted alkoxyaryl group, or a substituted or unsubstituted aralkyl group;
• W1 is independently at each occurrence —CH2—, —CH2—O—, —(C═O)—, —(C═O)—O—, —(C═O)—NH—, —(C═S)—, —(C═S)—NH—, or —CH2—S—;
• W2 is independently at each occurrence —O—, —CH2—or —S—;
• R2 is independently at each occurrence a bond, a bond to U, H, a substituted or unsubstituted C1-C30 alkyl group, a substituted or unsubstituted alkoxyaryl group, a substituted or unsubstituted aralkyl group, —NH2, —SH, C2-C4-alkene, C2-C4-alkyne, —NH(C═O)—CH2—Br, —(CH2)m-maleimide, or —N3,
• n is 1, 2 or 3;
• and
• m is 1-10;
• the peptide has a structure of Formula II:
• (SEQ. ID. NO. 1)
• aa1-aa2-aa3-aa4-aa5-aa6-aa7-aa8-aa9-aa10-aa11-aa12-
• aa13-aa14-aa15-aa16-aa17-aa18-aa19-aa20-aa21-aa22-
• aa23-aa24-aa25-aa26-aa27-aa28-aa29-aa30-aa31-aa32-
• aa33-aa34-aa35-aa36-aa37-Z Formula II
• wherein:
• Z is —OH or —NH—R3 , wherein R3 is H, substituted or unsubstituted C1-C12 alkyl, or a PEG chain of less than 10 Da;
• aa1 is His, N—Ac-His, pGlu-His, or N—R3-His;
• aa2 is Ser, Ala, Gly, Aib, Ac4c, or Ac5c;
• aa3 is Gln or Cit;
• aa4 is Gly or D-Ala;
• aa5 is Thr or Ser;
• aa6 is Phe, Trp, F2Phe, Me2Phe, or Nal2;
• aa7 is Thr or Ser;
• aa8 is Ser or Asp;
• aa9 is Asp or Glu;
• aa10 is Tyr, Leu, Met, Nal2, Bip, or Bip2EtMeO;
• aa11 is Ser, Asn, or U;
• aa12 is Lys, Glu, Ser, Arg, or U;
• aa13 is absent or Tyr, Gln, Cit, or U;
• aa14 is absent or Leu, Met, Nle, or U;
• aa15 is absent or Asp, Glu, or U;
• aa16 is absent or Ser, Gly, Glu, Aib, Ac5c, Lys, Arg, or U;
• aa17 is absent or Arg, hArg, Gln, Glu, Cit, Aib, Ac4c, Ac5c, or U;
• aa18 is absent or Arg, hArg, Ala, Aib, Ac4c, Ac5c, or U;
• aa19 is absent or Ala, Val, Aib, Ac4c, Ac5c, or U;
• aa20 is absent or Gln, Lys, Arg, Cit, Glu, Aib, Ac4c, Ac5c, or U;
• aa21 is absent or Asp, Glu, Leu, Aib, Ac4c, Ac5c, or U;
• aa22 is absent or Phe, Trp, Nal2, Aib, Ac4c, Ac5c, or U;
• aa23 is absent or Val, Ile, Aib, Ac4c, Ac5c, or U;
• aa24 is absent or Gln, Ala, Glu, Cit, or U;
• aa25 is absent or Trp, Nal2, or U;
• aa26 is absent or Leu or U;
• aa27 is absent or Met, Val, Nle, Lys, or U;
• aa28 is absent or Asn, Lys, or U;
• aa29 is absent or Thr, Gly, Aib, Ac4c, Ac5c, or U;
• aa30 is absent or Lys, Aib, Ac4c, Ac5c, or U;
• aa31 is absent or Arg, Aib, Ac4c, Ac5c, or U;
• aa32 is absent or Asn, Aib, Ac4c, Ac5c, or U;
• aa33 is absent or Arg, Aib, Ac4c, Ac5c, or U;
• aa34 is absent or Asn, Aib, Ac4c, Ac5c, or U;
• aa35 is absent or Asn, Aib, Ac4c, Ac5c, or U;
• aa36 is absent or Ala, Ile, Aib, Ac4c, Ac5C, or U;
• aa37 is absent or U;
• and
• U is a natural or unnatural amino acid comprising a functional group used for covalent attachment to the surfactant X;
• wherein any two of aa1-aa37 are optionally cyclized through their side chains to form a lactam linkage;
• and
• provided that one, or at least one, of aa11 -aa37 is the linker amino acid U covalently attached to the surfactant X.