Amide analogs of tridecapeptide ${alpha}$-factor (WHWLQLKPGQPMYCONH$_2$) of Saccharomyces cerevisiae, in which Trp at position 1 and 3 were replaced with other residues, were synthesized to ascertain whether cooperative interactions between two Trp residues occurred upon binding with its receptor. Analogs containing Ala or Aib at position 3 of the peptide $[Ala_3]{alpha}$-factor amide (2) and $[Aib_3]{alpha}$-factor amide (5) exhibited greater decreases in bioactivity than analogs with same residue at position one $[Ala^1]{alpha}$-factor amide (1) and $[Aib^1]{alpha}$-factor amide (4), reflecting that $Trp^3$ may plays more important role than $Trp^1$ for agonist activity. Analogs containing Ala or Aib in both position one and three 3, 6 exhibited complete loss of bioactivity, emphasizing both the essential role and the combined role of two indole rings for triggering cell signaling. In contrast, double substituted analog with D-Trp in both positions 9 exhibited greater activity than single substituted analog with D-Trp 8 or deleted analog 7, reflecting the combined contribution of two tryptophane residues of ${alpha}$-factor ligand to activation of Ste2p through interaction with residue $Tyr^{266}$ and importance of the proper parallel orientation of two indole rings for efficient triggering of signal G protein coupled activation. Among ten amide analogs, $[Ala^{1,3}]{alpha}$-factor amide (3), $[Aib^{1,3}]{alpha}$-factor amide (6), [D-$Trp^3]{alpha}$-factor amide (8) and [des-$Trp^1,Phe^3]{alpha}$-factor amide (10) were found to have antagonistic activity. Analogs 3 and 6 showed greater antagonistic activity than analogs 8 and 10.