Central residues of FSHβ (89–97) peptide are not critical for FSHR binding: Implications for peptidomimetic design

Prabhudesai, Kaushiki S.; Raje, Sahil; Desai, Karishma; Modi, Deepak; Dighe, Vikas; Contini, Alessandro; Idicula‐Thomas, Susan

doi:10.1016/j.bmcl.2021.128132

Cited by 3 publications

(3 citation statements)

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“…Bioinformatics has been widely and wisely used in the prediction of protein functions, gene recognition, determination of the physiological range of proteins, and prediction of advanced structure of protein to ensure that predicted results are accurate and efficient (Trevisan et al 2019;Song et al 2021;Brandes et al 2022). In the present study, the basic information of FSHβ protein was obtained by bioinformatics analysis for further studies (Bernard and Tran 2013;Prabhudesai et al 2021). Combined physicochemical properties of FSHβ protein showed that the protein was hydrophobic and did not have a transmembrane domain and also without the presence of signal peptide, which indicates that FSHβ protein may belong to wabbly hydrophilic non-secretory proteins (Kanasaki et al 2013;Wang et al 2021).…”

Section: Discussionmentioning

confidence: 88%

“…However, the FSHβ gene is linked to many other genes controlling pig litter size and is the main gene controlling this trait in pigs (Prabhudesai et al 2021). FSHβ plays a key role in follicular development and estrogen production in female animals, and the level of estrogen in the peripheral blood of sows and other animals during estrus is a decisive factor for their reproductive performance (Koketsu and Iida 2017;Gagnon et al 2018;Simon et al 2019).…”

Section: Introductionmentioning

confidence: 99%

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Analysis and Importance of FSH? Gene in Pig Reproductive Performance

2023

Int J Vet Sci

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FSHβ plays an important role in the reproductive performance of pigs, but there are no studies on its protein structure and function. In this study, bioinformatics tools were used to predict the physicochemical properties, secondary and tertiary structure, hydrophobicity/hydrophilicity, transmembrane domain, and sites of phosphorylation and glycosylation of signal peptide FSHβ protein of sows. The results showed that the number of amino acids of FSHβ was 185, that is, the theoretical isoelectric amino acid point was 53.8, the instability index was 46.23, and the average hydrophilicity coefficient was 0.732. FSHβ protein was found to be a hydrophobic protein without a transmembrane domain, with 33 phosphorylation sites. None of the signal peptides was found to be distributed in the inner complete sequence. The secondary structure was mainly composed of α-helix, extended strand, β-turn, and random coil, with values of 29.97, 27.53, 10.10 and 32.40%, respectively. In summary, this study suggests that the amino acid sequence (988~1146aa) of FSHβ can be used to express antigens. It provides a reliable basis for further study of FSHβ protein function, purification of FSHβ protein, preparation of FSHβ antibody, and drug screening to improve reproductive performance of pigs.

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Section: Discussionmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Analysis and Importance of FSH? Gene in Pig Reproductive Performance

2023

Int J Vet Sci

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“…The lower affinity (higher Kd) of FSH-β-(89-97) could be due to the smaller surface of interaction and capacity to emulate the native structure of a shorter peptide (15 mer vs 9 mer). Interestingly, Prabhudesai et al also showed that the residues 91-STDC-94 could be substituted with alanine (AAAA), suggesting that the central residues of FSH-β- (89)(90)(91)(92)(93)(94)(95)(96)(97) are not critical for FSH-binding 67 ; this alanine analog had less inhibitory activity. These results agree with the PISA server data of Table 2, showing that amino acids 91 and 92 do not contribute to the buried surface area (BSA) in the interaction with FSHR, and therefore, are not directly involved in binding.…”

Section: Comparison Between the Predicted Binding Regions Of Fsh-β Wi...mentioning

confidence: 99%

Overlapping synthetic peptides as a tool to map protein-protein interactions ̶ FSH as a model system of nonadditive interactions

Santa‐Coloma

2022

Biochimica et Biophysica Acta (BBA) - General Subjects

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Novel Polymyxin-Inspired Peptidomimetics Targeting the SARS-CoV-2 Spike:hACE2 Interface

Bugatti

Sartori

Battistini

et al. 2023

IJMS

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Though the bulk of the COVID-19 pandemic is behind, the search for effective and safe anti-SARS-CoV-2 drugs continues to be relevant. A highly pursued approach for antiviral drug development involves targeting the viral spike (S) protein of SARS-CoV-2 to prevent its attachment to the cellular receptor ACE2. Here, we exploited the core structure of polymyxin B, a naturally occurring antibiotic, to design and synthesize unprecedented peptidomimetics (PMs), intended to target contemporarily two defined, non-overlapping regions of the S receptor-binding domain (RBD). Monomers 1, 2, and 8, and heterodimers 7 and 10 bound to the S-RBD with micromolar affinity in cell-free surface plasmon resonance assays (KD ranging from 2.31 μM to 2.78 μM for dimers and 8.56 μM to 10.12 μM for monomers). Although the PMs were not able to fully protect cell cultures from infection with authentic live SARS-CoV-2, dimer 10 exerted a minimal but detectable inhibition of SARS-CoV-2 entry in U87.ACE2+ and A549.ACE2.TMPRSS2+ cells. These results validated a previous modeling study and provided the first proof-of-feasibility of using medium-sized heterodimeric PMs for targeting the S-RBD. Thus, heterodimers 7 and 10 may serve as a lead for the development of optimized compounds, which are structurally related to polymyxin, with improved S-RBD affinity and anti-SARS-CoV-2 potential.

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Central residues of FSHβ (89–97) peptide are not critical for FSHR binding: Implications for peptidomimetic design

Cited by 3 publications

References 46 publications

Analysis and Importance of FSH? Gene in Pig Reproductive Performance

Analysis and Importance of FSH? Gene in Pig Reproductive Performance

Overlapping synthetic peptides as a tool to map protein-protein interactions ̶ FSH as a model system of nonadditive interactions

Novel Polymyxin-Inspired Peptidomimetics Targeting the SARS-CoV-2 Spike:hACE2 Interface

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