Table 4.
Mutations of residues 27–37
| Residue | Mutation | Effect | Comment | Reference |
|---|---|---|---|---|
| Phe27 | [Phe27]-CGRP27–37 | Eightfold decrease in affinity | SK-N-MC cells | (Rist et al., 1998) |
| Val28 | [Ala28]-Tyr0CGRP27–37 | Threefold decrease in affinity | SK-N-MC cells | (Rist et al., 1998) |
| Pro29 | [Ala29]-Tyr0CGRP27–37 | No binding | SK-N-MC cells | (Rist et al., 1998) |
| Pro29 | [Ala29Ala34Phe35]-CGRP27–37 | Sevenfold decrease in affinity | SK-N-MC cells | (Carpenter et al., 2001) |
| Pro29 | [▴29D31P34F35]-CGRP27−37 | No change in affinity compared with CGRP8–37 | SK-N-MC cells | (Lang et al., 2006) |
| Thr30 | [Ala30]-Tyr0CGRP27–37 | No binding | SK-N-MC cells | (Rist et al., 1998) |
| Thr30 | [Ser30]-Tyr0CGRP27–37 | >30-fold decrease in affinity | SK-N-MC cells | (Rist et al., 1998) |
| Thr30 | [Ala30Ala34Phe35]-CGRP27–37 | 100-fold less potent than [Ala34Phe35]-CGRP27–37 | SK-N-MC cells | (Carpenter et al., 2001) |
| Asn31 | [Ala31]-Tyr0CGRP27–37 | >30-fold decrease in affinity | SK-N-MC cells | (Rist et al., 1998) |
| Asn31 | [Leu31]-Tyr0CGRP27–37 | Twofold decrease in affinity | SK-N-MC cells | (Rist et al., 1998) |
| Asn31 | [Gln31]-Tyr0CGRP27–37 | 30-fold decrease in affinity | SK-N-MC cells | (Rist et al., 1998) |
| Asn31 | [Asp31]-Tyr0CGRP27–37 | Twofold decrease in affinity | SK-N-MC cells | (Rist et al., 1998) |
| Asn31 | [Ala31Ala34Phe35]-CGRP27–37 | Fivefold less potent than [Ala34Phe35]-CGRP27–37 | SK-N-MC cells | (Carpenter et al., 2001) |
| Val32 | [Ala32]-Tyr0CGRP27–37 | No binding | SK-N-MC cells | (Rist et al., 1998) |
| Val32 | [Ala32Ala34Phe35]-CGRP27–37 | 240-fold decrease in affinity compared with [Ala34Phe35]-CGRP27–37 | SK-N-MC cells | (Carpenter et al., 2001) |
| Gly33 | [Ala33]-Tyr0CGRP27–37 | No binding | SK-N-MC cells | (Rist et al., 1998) |
| Gly33 | [Ala33Ala34Phe35]-CGRP27–37 | 23-fold decrease in affinity | SK-N-MC cells | (Carpenter et al., 2001) |
| Gly33 | [Asp31,azaGly33,Pro34,Phe35]-CGRP29–37 | No binding | CGRP receptor, HEK293 cells | (Boeglin et al., 2007) |
| Gly33 | [Asp31,azaGly33,Pro34,Phe35]-CGRP27–37 | 10-fold increase in affinity compared with [Asp31,Pro34,Phe35]-CGRP27–37 | CGRP receptor, HEK293 cells | (Boeglin et al., 2007) |
| Ser34 | [Ala34]-Tyr0CGRP27–37 | No change in affinity | SK-N-MC cells | (Rist et al., 1998) |
| Ser34 | [D31▾34F35]- CGRP8−37 | Threefold decrease in affinity compared with CGRP8–37 | SK-N-MC cells | (Lang et al., 2006) |
| Glu35 | [Ala35]-Tyr0CGRP27–37 | Threefold decrease in affinity | SK-N-MC cells | (Rist et al., 1998) |
| Glu35 | [His35]-Tyr0CGRP27–37 | No change in affinity | SK-N-MC cells | (Rist et al., 1998) |
| Glu35 | [Gln35]-Tyr0CGRP27–37 | Twofold decrease in affinity | SK-N-MC cells | (Rist et al., 1998) |
| Glu35 | [Leu35]-Tyr0CGRP27–37 | Threefold decrease in affinity | SK-N-MC cells | (Rist et al., 1998) |
| Glu35 | [Ala35Ala34Phe35]-CGRP27–37 | 14-fold less potent than [Ala34Phe35]-CGRP27–37 | SK-N-MC cells | (Carpenter et al., 2001) |
| Ala36 | [Phe36]-Tyr0CGRP27–37 | No binding | SK-N-MC cells | (Rist et al., 1998) |
| Ala36 | [Gly36]-Tyr0CGRP27–37 | 16-fold decrease in affinity | SK-N-MC cells | (Rist et al., 1998) |
| Phe37 | [Ala37]-Tyr0CGRP27–37 | No binding | SK-N-MC cells | (Rist et al., 1998) |
| Phe37 | [Tyr37]-Tyr0CGRP27–37 | 11-fold decrease in affinity | SK-N-MC cells | (Rist et al., 1998) |
| Phe37 | [Ala37Ala34Phe35]-CGRP27–37 | >340-fold decrease in affinity compared with [Ala34Phe35]-CGRP27–37 | SK-N-MC cells | (Carpenter et al., 2001) |
| Phe37 | [Gly37]-CGRP8–37 | 2050-fold decrease in affinity of CGRP8–37 | Porcine coronary artery | (Smith et al., 2003) |
| Phe37 | [Tyr37]-CGRP8–37 | No decrease in affinity of CGRP8–37 | Porcine coronary artery | (Smith et al., 2003) |
| Phe37 | Replacement by rotational restricted Phe analogues | 40–60-fold decrease in affinity of CGRP8–37 | Porcine coronary artery | (Smith et al., 2003) |
| Phe37 | [Ala37]-CGRP8–37 | >100-fold decrease in affinity of CGRP8–37 | Rat pulmonary artery | (Wisskirchen et al., 2000) |
| Asn31Ser34Glu35 | [Asp31Ala34Phe35]-CGRP27–37 | 10-fold decrease in affinity compared with CGRP | SK-N-MC cells | (Carpenter et al., 2001) |
| Asn31Ser34Glu35 | [Asp31Phe34Phe35]-CGRP27–37 | Twofold decrease in affinity compared with CGRP | SK-N-MC cells | (Carpenter et al., 2001) |
| Ser19Gly20 and Gly33Ser34 | Both replaced by BTD | No decrease in affinity | Rat pulmonary artery | (Wisskirchen et al., 2000) |
| Residues 1–27 | CGRP27–37 | 16000-fold decrease in affinity compared with CGRP8–37 | SK-N-MC cells | (Ladram et al., 2008) |
| Residues 1–27 | Tyr0-CGRP19–37 | 900-fold decrease in affinity to CGRP8-37 | SK-N-MC cells | (Heino et al., 1998) |
| Phyllomedusa CGRP27–37 | Residues 1–28 | Ki 95 nM (fivefold less potent than human CGRP) | SK-N-MC cells | (Ladram et al., 2008) |
Unless otherwise stated, all differences are with respect to the parent compound used to create the analogue: human α-CGRP27–37, Tyr°CGRP27–37 or CGRP8–37. ▾, ▴: the ▾ and ▴ conformers of β-aminocyclopropane carboxylic acid.
BTD, β-turn dipeptide.