GRF analogs II

A method of stimulating the release of growth hormone in an animal, which comprises administering to said animal an effective amount of a synthetic peptide having the formula:

• R.sub.1 -Ala-R.sub.3 -Ala-Ile-Phe-Thr-R.sub.8 -Ser-R.sub.10 -Arg-R.sub.12 -R.sub.13 -Leu-R.sub.15 -Gln-Leu-R.sub.18 -Ala-Arg-Lys-Leu-Leu-R.sub.24 -R.sub.25 -Ile-R.sub.27 -R.sub.28 -Arg-Gln-Gln-Gly-Glu-R.sub.34 -Asn-Gln-Glu-R.sub.38 -R.sub.39 -R.sub.40 -Arg-R.sub.42 -R.sub.43 -R.sub.44 -Y wherein R.sub.1 is Tyr, D-Tyr, Met, Phe, D-Phe, pCl-Phe, Leu, His or D-His, which residue has either a C.sup.a Me or N.sup.a Me substitution;
• R.sub.3 is Asp or D-Asp;
• R.sub.8 is Ser, Asn D-Ser or D-Asn;
• R.sub.10 is Tyr or D-Tyr;
• R.sub.12 is Arg or Lys;
• R.sub.13 is Ile or Val;
• R.sub.15 is Gly or D-Ala;
• R.sub.18 is Tyr or Ser;
• R.sub.24 is His or Gln;
• R.sub.25 is Glu or Asp;
• R.sub.27 is Met, Ala, Nle, Ile, Leu, Nva or Val;
• R.sub.28 is Asn or Ser;
• R.sub.34 is Arg or Ser;
• R.sub.38 is Gln or Arg;
• R.sub.39 is Arg or Gly;
• R.sub.40 is Ser or Ala;
• R.sub.42 is Phe or Ala;
• R.sub.43 is Asn or Arg;
• R.sub.44 is Leu or Val;
• and Y is the carboxyl moiety of the amino acid residue at the C-terminus, which is the radical --COOR,--CRO,--CONHNHR, --CON(R)(R') or -CH.sub.2 OR, with R and R' being lower alkyl, fluoro lower alkyl or hydrogen;
• or a biologically active fragment thereof extending from the N-terminus to a residue in any of positions 27 through 43 as its C-terminus;
• or a nontoxic acid addition salt thereof.

A method of accelerating growth in non-human animals, which method comprises administering an effective amount of a synthetic peptide having the sequence:

• R.sub.1 -Ala-R.sub.3 -Ala-Ile-Phe-Thr-R.sub.8 -Ser-R.sub.10 -Arg-R.sub.12 -R.sub.13 -Leu-R.sub.15 -Gln-Leu-R.sub.18 -Ala-Arg-Lys-Leu-Leu-R.sub.24 -R.sub.25 -Ile-R.sub.27 -R.sub.28 -R.sub.29 wherein R.sub.1 is Tyr, D-Tyr, Met, Phe, D-Phe, pCl-Phe, Leu, His or D-His which residue has either a C.sup.a Me or N.sup.a Me substitution;
• R.sub.3 is Asp or D-Asp;
• R.sub.8 is Ser, Asn, D-Ser or D-Asn;
• R.sub.10 is Tyr or D-Tyr;
• R.sub.12 is Arg or Lys:
• R.sub.13 is Ile or Val;
• R.sub.15 is Gly or D-Ala;
• R.sub.18 is Tyr or Ser;
• R.sub.24 is His or Gln;
• R.sub.25 is Glu or Asp;
• R.sub.27 is Met, Ala, Nle, Ile, Leu, Nva or Val;
• R.sub.28 is Asn, Ser or des-R.sub.28 ;
• and R.sub.29 is Arg or des-R.sub.29, or a nontoxic acid addition salt thereof.

A synthetic peptide having the formula:

• R.sub.1 -Ala-R.sub.3 -Ala-Ile-Phe-Thr-R.sub.8 -Ser-R.sub.10 -Arg-R.sub.12 -R.sub.13 -Leu-R.sub.15 -Gln-Leu-R.sub.18 -Ala-Arg-Lys-Leu-Leu-R.sub.24 -R.sub.25 -Ile-R.sub.27 -R.sub.28 -R.sub.29 -R.sub.30 -R.sub.31 -R.sub.32 -Y wherein R.sub.1 is Tyr, D-Tyr, Met, Phe, D-Phe, pCl-Phe, Leu, His or D-His which residue has either a C.sup.a Me or N.sup.a Me substitution;
• R.sub.3 is Asp or D-Asp;
• R.sub.8 is Ser, Asn, D-Ser or D-Asn;
• R.sub.10 is Tyr or D-Tyr;
• R.sub.12 is Arg or Lys;
• R.sub.13 is Ile or Val;
• R.sub.15 is Gly or D-Ala;
• R.sub.18 is Tyr or Ser;
• R.sub.24 is His or Gln;
• R.sub.25 is Glu or Asp;
• R.sub.27 is Met, Ala, Nle, Ile, Leu, Nva or Val;
• R.sub.28 is Asn, Ser or des-R.sub.28 ;
• R.sub.29 is Arg or des-R.sub.29;
• R.sub.30 is Gln or des-R.sub.30 ;
• R.sub.31 is Gln or des-R.sub.31 ;
• R.sub.32 is Gly or des-R.sub.32 ;
• and Y is CON(R)(R') with R and R' being lower alkyl, fluoro lower alkyl or hydrogen;
• or a nontoxic acid addition salt thereof.