Identification of selective and non-selective, biostable beta-amino acid agonists of recombinant insect kinin receptors from the southern cattle tick Boophilus microplus and mosquito Aedes aegypti.
The multifunctional arthropod 'insect kinins' share the evolutionarily conserved C-terminal pentapeptide motif Phe-X1-X2-Trp-Gly-NH2, where X1=His, Asn, Ser, or Tyr and X2=Ser, Pro, or Ala. Eight different analogs of the insect kinin C-terminal pentapeptide active core in which the critical residues Phe 1, Pro3 and Trp 4 are replaced with beta 3-amino acid and/or their beta2-amino acid counterparts were evaluated on recombinant insect kinin receptors from the southern cattle tick, Boophilus microplus (Canestrini) and the dengue vector, the mosquito Aedes aegypti (L.). A number of these analogs previously demonstrated enhanced resistance to degradation by peptidases. Single-replacement analog beta 2 Trp 4 and double-replacement analog [beta 3 Phe 2, beta 3 Pro 3] of the insect kinins proved to be selective agonists for the tick receptor, whereas single-replacement analog beta 3 Pro 3 and double-replacement analog [beta 3 Phe, beta 3 Pro 3] were strong agonists on both mosquito and tick receptors. These biostable analogs represent new tools for arthropod endocrinologists and potential leads in the development of selective, environmentally friendly arthropod pest control agents capable of disrupting insect kinin-regulated processes.
Taneja-Bageshwar
Suparna
S
Department of Entomology, Texas A&M University, College Station, TX 77843, USA.
Strey
Allison
A
Zubrzak
Pawel
P
Williams
Howard
H
Reyes-Rangel
Gloria
G
Juaristi
Eusebio
E
Pietrantonio
Patricia
P
Nachman
Ronald J
RJ
D000330:Aedes / Q000235:genetics / Q000378:metabolism; D000331:Aequorin / Q000235:genetics; D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D060829:Arthropod Proteins; D016466:CHO Cells; D020013:Calcium Signaling / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D019476:Insect Proteins / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D007705:Kinins / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D009479:Neuropeptides / Q000737:chemistry / Q000494:pharmacology*; D018013:Receptors, Neuropeptide / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000819:agonists / Q000378:metabolism; D048494:Rhipicephalus / Q000235:genetics / Q000378:metabolism; D013237:Stereoisomerism; D014162:Transfection
D000596:Amino Acids; D060829:Arthropod Proteins; D019476:Insect Proteins; D007705:Kinins; D009479:Neuropeptides; D018013:Receptors, Neuropeptide; D011994:Recombinant Proteins; C419691:leucokinin-like peptide receptor, cattle tick; D000331:Aequorin