Stabilized therapeutic small helical antiviral peptides

An isolated peptide from 10 to 23 amino acids long, wherein the sequence of the amino acids of the isolated peptide comprises (I/L/V)(T/S/A/V/C)(F/I/L/V/Y/M/W)(D/E/S)(D/E)(L/F/I/V/Y/M/W)(L/D/T/F/I/V/Y/M/W)(D/E/A/S)(Y/F/I/L/V/M/W)(Y/F/I/L/V/M/T) (SEQ ID NO:2), wherein two of the amino acids are unnatural amino acids having either R or S stereochemistry at the α-carbon, wherein the unnatural amino acids are each (S)-α-2-(4′-pentenyl)alanine or (S)-α-2-(7′-octenyl)alanine,

• wherein the α-carbon of the unnatural amino acids comprises a methyl group and an olefinic group, where the two olefinic groups of the unnatural amino acids are on the same side of the α-helix and are joined to form a cross-link between the two unnatural amino acids,
• wherein the two unnatural amino acids replace two of the amino acids at any positions selected from the group consisting of 4 amino acids apart (i and i+4) and 7 amino acids apart (i and i+7);
• and
• wherein the cross-link between the two unnatural amino acids is a C1-C10 alkyl, alkenyl, alkynyl, or (R1-K-R1)n;
• each of which is substituted with a 0-6 R2,
• wherein R1 is an alkyl, alkenyl, or alkynyl;
• K is O, S, SO, SO2, CO, CONR4, or
• R2 is a halo, C1-C10 alkyl, OR3, N(R3)2, SR3SOR3, SO2R3, CO2R3, R3, a fluorescent moiety, or a radioisotope;
• R3 is H or a C1-C10 alkyl;
• R4 is H, alkyl, or a therapeutic agent;
• and
• n is an integer from 1-4.