Compositions and methods for modulating connexin hemichannels

A method of modulating a hemichannel in a cell, tissue or organ exposed to stress, the method comprising contacting the stressed cell, tissue or organ with a therapeutically effective amount of at least one compound selected from the group consisting of compounds represented as Formula I or II, wherein the contact is sufficient to modulate the hemichannel in the stressed cell, tissue or organ, wherein Formula I is defined as follows:

• wherein
• R1 represents H or acetyl (Ac)
• R2 represents a sidechain of one of the amino acids Gly, Tyr, D-Tyr, Phe and D-Phe,
• R3 represents any amino acid sidechain,
• R4 represents a sidechain of one of the amino acids Gly, Tyr, D-Tyr, Phe and D-Phe,
• R5 represents OH or NH2,
• and a, S, T, P and Q are integers and independently=0 or 1;
• and salts thereof,
• and wherein Formula II is defined as follows:
• R1-X1-X2-X3-R2
• wherein,
• X1 is 0, Ala, Gly, β-Ala, Tyr, D-Tyr, Asp,
• X2 is 0, Ala-Gly-T4c-Pro, Ala-Sar-Hyp-Pro, Ala-Asn, D-Asn-D-Ala, D-Asn, Gly, Ala, D-Ala, β-Ala, Asn or,
• X3 is Tyr, D-Tyr, Gly or Phe, and
• R1 is H or Ac,
• R2 is OH or NH2,
• with the proviso that X1 and X2 are not both 0;
• and salts thereof.