Synthesis of achatin-I (Gly-D-Phe-l-Ala-l-Asp) analogs having dehydrophenylalanine or aminoisobutyric acid residue at position 2, and their effects on Achatina giant neurons

Emaduddin, Muhammad ; Takeuchi, Hiroshi ; Jain, Ratan Mani ; Chauhan, Virender Singh (1997) Synthesis of achatin-I (Gly-D-Phe-l-Ala-l-Asp) analogs having dehydrophenylalanine or aminoisobutyric acid residue at position 2, and their effects on Achatina giant neurons General Pharmacology: The Vascular System, 28 (2). pp. 265-267. ISSN 0306-3623

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Official URL: http://www.sciencedirect.com/science/article/pii/S...

Related URL: http://dx.doi.org/10.1016/S0306-3623(96)00170-X

Abstract

1. 1. Achatin-I (Gly-D-Phe-L-Ala-L-Asp), a neuroactive tetrapeptide having a D-phenyl-alanine residue, has been proposed to be an excitatory neurotransmitter of Achatina giant neurons. It was revealed that the D-Phe2 residue is essential for bioactivity of achatin-I, which seems to adopt β-turn conformation. In the present study, in order to investigate the structure-activity relationships of achatin-I and its derivatives, the two highly constrained analogs of achatin-I, [ΔZPhe2]achatin-I (Gly-ΔZPhe-L-Ala-L-Asp) (ΔZPhe: (Z)-α,β-dehydrophenylalanine) and [Aib2]achatin-I (Gly-Aib-L-Ala-L-Asp) (Aib: α-aminoisobutyric acid), were synthesized, and their effects on the two identifiable Achatina giant neuron types, PON (periodically oscillating neuron) and v-RCDN (ventral-right cerebral distinct neuron), were examined in comparison with those of achatin-I under voltage clamp. 2. 2. Achatin-I (n = 6), ejected onto the neurone by brief pneumatic pressure (2 kg/cm2, 400 ms, 10-3 M, at 10-min intervals), produced an inward current (Ii) on PON. The Ii value (mean ± SEM) was 0.44±0.03 nA. The interval between the achatin-I ejection and the Ii peak was 14.74±3.15 s (n=6). [ΔZPhe2]achatin-I (n=6) and [Aib2]achatin-I (n=6) had no effect on this neuron type. 3. 3. On the other hand, achatin-I (n=10) and [ΔZPhe2]-achatin-I (n=10), ejected by brief pressure, produced an Iin on v-RCDN. The Iin values were 0.85±0.07 nA for achatin-I and 0.48±0.05 nA (p<0.01, compared with that of achatin-I by Student's t-test for paired data) for [ΔZPhe2]achatin-I. The intervals between the compound ejection and the Iin peak were 5.95±0.33 s for achatin-I and 8.70±0.81 s (p<0.05, compared with that of achatin-I) for [ΔZPhe2]achatin-I. [Aib2]achatin-I (n=10) had no effect on this neuron type.

Item Type:Article
Source:Copyright of this article belongs to Elsevier Science.
Keywords:Neuropeptide; Achatin-I (Gly-D-Phe-L-Ala-L-Asp); Analogs; α; β-dehydrophenylalanine; α-aminoisobutyric Acid; Giant Neuron; Snail (Achatina fulica Férussac)
ID Code:77478
Deposited On:12 Jan 2012 14:40
Last Modified:12 Jan 2012 14:40

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