Biological activity and receptor binding properties of some modified analogues of FMRFamide

Geraghty, Robert F.; Irvine, G. Brent; Williams, C. H.; Cottrell, G. A.

doi:10.1016/0196-9781(94)90173-2

Cited by 12 publications

(2 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Peptide aldehydes have particular functional significance in some cases (20,44). Geraghty et al in a systematic study of C-terminal modification similar to our study reported that the activity of a molluscan FMRFamide, both in vitro and in vivo, was unaffected by a methylamide or dimethylamide substitution but was diminished ∼30-fold by an alcohol one (45). Thus, to date, there is no pattern in the effects of C-terminal modification of peptides on their bioactivities.…”

Section: Discussionsupporting

confidence: 66%

C-Terminal Analogues of Parathyroid Hormone: Effect of C-Terminus Function on Helical Structure, Stability, and Bioactivity

et al. 2006

View full text Add to dashboard Cite

We have studied the effects of C-terminal group modifications (amide, methylamide, dimethylamide, aldehyde, and alcohol) on the conformation, adenylyl cyclase stimulation (AC), or binding of parathyroid hormone (hPTH) analogues, hPTH(1-28)NH(2) and hPTH(1-31)NH(2). hPTH(1-31)NH(2) has a C-terminal alpha-helix bounded by residues 17-29 [Chen, Z., et al. (2000) Biochemistry 39, 12766]. In both cases, relative to the natural analogue with a carboxyl C-terminus, the amide and methylamide had increased helix content whereas the dimethylamide forms had CD spectra more similar to the carboxyl one. Conformational effects were more pronounced with hPTH(1-28) than with hPTH(1-31), with increases in helix content of approximately 30% in contrast to 10%. Stabilization of the C-terminal helix of residues 1-28 seemed to correlate with an ability of the C-terminal function to H-bond appropriately. None of the analogues affected the AC stimulating activity significantly, but there was an up to 15-fold decrease in the level of apparent binding of the carboxyl hPTH(1-28) analogue compared to that of the methylamide and a 4-fold decrease in the level of binding of the aldehyde or dimethylamide. There was no significant change in binding activities for the 1-31 analogues. These observations are consistent with previous studies that imply the importance of a region of the hormone's C-terminal alpha-helix for tight binding to the receptor. They also show that modulation of helix stability does have an effect on the binding of the hormone, but only when the C-terminus is at the putative end of the helix. The similarity of AC stimulation even when binding changed 10-fold can be explained by assuming greater efficacy of the weaker binding PTH-receptor complexes in stimulating AC.

show abstract

Section: Discussionsupporting

confidence: 66%

C-Terminal Analogues of Parathyroid Hormone: Effect of C-Terminus Function on Helical Structure, Stability, and Bioactivity

et al. 2006

View full text Add to dashboard Cite

show abstract

“…Based on (i) the conserved motifs in predicted nlp neuropeptides and (ii) similar ESTs͞neuropeptides in other species, families of related neuropeptide genes were constructed. Experimental evidence suggests that the level of homology over an entire neuropeptide is less important than the presence of a specific, conserved motif within the bioactive neuropeptide (33)(34)(35)(36). Therefore, nlp genes were initially grouped into families based on 3-to 5-aa motifs found in predicted nlp neuropeptides.…”

Section: Search Patterns Were Permutations Of [Kr]-[kr]-x(320)-[kr]-mentioning

confidence: 99%

Identification of neuropeptide-like protein gene families in Caenorhabditis elegans and other species

Nathoo

Moeller

Westlund

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

308

303

View full text Add to dashboard Cite

Neuropeptides play critical roles in synaptic signaling in all nervous systems. Unlike classical neurotransmitters, peptidergic neurotransmitters are encoded as preproproteins that are posttranslationally processed to yield bioactive neuropeptides. To identify novel peptidergic neurotransmitters, the Caenorhabditis elegans genome was searched for predicted proteins with the structural hallmarks of neuropeptide preproproteins. Thirty-two C. elegans neuropeptide-like protein (nlp) genes were identified. The nlp genes define at least 11 families of putative neuropeptides with unique motifs; similar expressed sequence tags were identified in other invertebrate species for all 11 families. Six of these families are defined by putative bioactive motifs (FAFA, GGxYamide, MRxamide, LQFamide, LxDxamide, and GGARAF); the remaining five families are related to allatostatin, myomodulin, buccalin͞drosul-fakinin, orcokinin, and APGWamide neuropeptides (MGL͞Famide, FRPamide, MSFamide, GFxGF, and YGGWamide families, respectively). Most C. elegans nlp gene expression is in neurons. The C. elegans nlp genes and similar genes encoding putative neuropeptides in other species are likely to play diverse roles in nervous system function. C hemical signaling via neurotransmitters is critical for synaptic transmission of information between neurons. Neuropeptides are the most varied and numerous type of neurotransmitters. Invertebrate neuropeptides are thought primarily to modulate synaptic function of classical small-molecule neurotransmitters by means of seven transmembrane domain receptors. However, the recent identification of a FMRFamide-gated sodium channel from Helix lucorum suggests that they may also act as fast transmitters (1). In mammals, neuropeptides and their receptors are implicated in behaviors including feeding and sleep (2-5). Despite their clear roles in synaptic signaling and behavior, neuropeptide functions are still not understood.Biochemical isolation of neuropeptides has been relatively successful in several invertebrate systems, including Lymnaea stagnalis, Drosophila melanogaster, and Aplysia californica (6-8), and has led to the identification of several invertebrate neuropeptide families. In the nematode Caenorhabditis elegans, 23 FMRFamide-related proteins (FaRP) neuropeptide genes, designated flp-1 to flp-23 (FMRFamide-like proteins), have been identified (9). Only flp-1 has been characterized at the functional level. Animals lacking flp-1 have abnormal behavior, including uncoordinated movement and hyperactivity (10). The only other C. elegans non-flp neuropeptide genes that have been identified are the 37 insulin-like genes (11, 12).Dense-core synaptic vesicles are prevalent in presynaptic terminals of C. elegans neurons that are neither FaRP immunoreactive nor catecholaminergic (13), suggesting that nonFaRP neuropeptides are present. Additionally, about 130 genes encoding putative neuropeptide receptors were identified in the C. elegans genome (14). This large number of receptors is much higher than the...

show abstract

Characterization of binding of the annelidan myoactive peptides, GGNG peptides, to tissues of the earthworm,Eisenia foetida

et al. 1997

View full text Add to dashboard Cite

The GGNG peptides are myoactive peptides which we have isolated from several species of annelids. Two types of peptides have been isolated as GGNG peptides: earthworm excitatory peptides (EEP) and leech excitatory peptide (LEP). The EEP and LEP are highly homologous with each other but act specifically on earthworms and leeches, respectively. To approach the mechanism of the specific action, we attempted to characterize the receptors for EEP in the earthworm Eisenia foetida, from which EEP have been isolated, by a radioreceptor assay. To prepare a radiolabeled ligand, we first coupled EEP to Bolton‐Hunter reagent and then labeled it with 125I ([125I] BH‐EEP). Binding of the [125I] BH‐EEP to the membrane preparation of the earthworm tissue (crop‐gizzard) was reversible, saturable, and specific with a Kd of 4.9 ± 1.2 nM and a Bmax of 15.9 ± 2.0 fmol/mg wet tissue. For the earthworm membrane preparation, EEP showed a much greater potency than LEP in displacing [125I] BH‐EEP, suggesting that the earthworm tissues contain EEP‐specific receptors. This result would account for the specific biological activity of EEP and LEP on the earthworm and leech tissues, respectively. The binding capacity was high in the anterior part of digestive tract including the esophagus, crop and gizzard, and the nephridia. From these results, together with the observed myotropic activity of EEP on gut tissues, it is assumed that EEP is physiologically involved in regulation of the gut motility in the earthworm E. foetida. J. Exp. Zool. 279:562–570, 1997.© 1997 Wiley‐Liss, Inc.

show abstract

Biological activity and receptor binding properties of some modified analogues of FMRFamide

Cited by 12 publications

References 24 publications

C-Terminal Analogues of Parathyroid Hormone: Effect of C-Terminus Function on Helical Structure, Stability, and Bioactivity

C-Terminal Analogues of Parathyroid Hormone: Effect of C-Terminus Function on Helical Structure, Stability, and Bioactivity

Identification of neuropeptide-like protein gene families in Caenorhabditis elegans and other species

Characterization of binding of the annelidan myoactive peptides, GGNG peptides, to tissues of the earthworm,Eisenia foetida

Contact Info

Product

Resources

About