Contrasting solution conformations of peptides containing α,α-dialkylated residues with linear and cyclic side chains

The conformational properties of α,α-dialkylated amino acid residues possessing acyclic (diethylglycine, Deg: di-n-propylglycine, Dpg; di-n-butylglycine, Dbg) and cyclic (1-amino-cycloalkane-1-carboxylic acid, Acnc) side chains have been compared in solution. The five peptides studied by nmr and CD spectroscopy are Boc-Ala-Xxx-Ala-OMe, where Xxx = Deg(I). Dpg (II), Dbg (III), Ac6c (IV), and Ac7c (V). Delineation of solvent-shielded NH groups have been achieved by solvent and temperature dependence of NH chemical shifts in CDCl3 and (CD3)2SO and by paramagnetic radical induced line broadening in pepiide III. In the Dxg peptides the order of solvent exposure of NH groups is Ala(1) > Ala(3) > Dxg(2), whereas in the Acnc peptides the order of solvent exposure of NH groups is Ala(1) > Acnc(2) > Ala(3). The nmr results suggest that Acnc peptides adopt folded β-turn conformations with Ala(1) and Acnc(2) occupying i + 1 and i + 2 positions. In contrast, the Dxg peptides favor extended C5 conformations. The conformational differences in the two series are clearly borne out in CD studies. The solution conformations of peptides I-III are distinctly different from the β-turn structure observed in crystals. Low temperature nmr spectra recorded immediately after dissolution of crystals of peptide II provide evidence for a structural transition. Introduction of an additional hydrogen-bonding function in Boc-Ala-Dpg-Ala-NHMe (VI) results in a stabilization of a consecutive β-turn or incipient 310-helix in solution

Factors Influencing Adoption of Climate-Friendly Oxo-Biodegradable Jan Ausadhi Suvidha Sanitary Napkins among Women in India

With the aim of making and providing generic drugs available at a cheap cost to everyone across the country, "Pradhan Mantri Bhartiya Jan Ausadhi Pariyojana (PMBJP) was launched and under this PMBJP (can be translated in English as Prime Minister Indian Mass Medicine Scheme) scheme, Jan Ausadhi Suvidha Sanitary Napkins were launched to provide biodegradable sanitary napkins at less price for women of the country. Menstruation is a part of women’s life and menstrual hygiene product is the basic need for women to face this menstruation period. There are many health issues that were faced by women during menstruation and the sanitary napkins used during menstruation causes different pollution. For the purpose of safeguarding the health, financial affordability of Indian women this suvidha sanitary napkin was launched. Earlier in rural areas by abandoning non-biodegradable sanitary napkin a lot of pollution was caused but now it is under check. In order to assess the “Factors influencing adoption of climate-friendly Oxo- biodegradable Jan Ausadhi Suvidha Sanitary Napkins among women in India” Muzaffarpur district of Bihar was selected as locale of research and two blocks Muraul and Sakra have been selected for the study, as these blocks found with established structures of Jan Ausadhi Kendras. From each blocks 40 respondents were selected and all these selected respondents known to this scheme or having experience in using Jan Ausadhi Suvidha Sanitary napkins. So, total number of respondents were 80. Statistical tool such as Binary logistic analysis revealed that Profession and Annual income were significant at 5 percent level and variables like AWARE PMBJP and Marital status were significant at 10 percent level and all significant factors determine the adoption of climate-friendly bio-degradable Jan Ausadhi Suvidha Sanitary Napkins. The result of the study of the impact on women will surely be used to enhance the health status of women and also compliment Swachh Bharat Abhiyan

Contrasting solution conformations of peptides containing alpha,alpha-dialkylated residues with linear and cyclic side chains

The conformational properties of , -dialkylated amino acid residues possessing acyclic (diethylglycine, Deg: di-n-propylglycine, Dpg; di-n-butylglycine, Dbg) and cyclic (1-amino-cycloalkane-1-carboxylic acid, Acnc) side chains have been compared in solution. The five peptides studied by nmr and CD spectroscopy are Boc-Ala-Xxx-Ala-OMe, where Xxx = Deg(I). Dpg (II), Dbg (III), Ac6c (IV), and Ac7c (V). Delineation of solvent-shielded NH groups have been achieved by solvent and temperature dependence of NH chemical shifts in CDCl3 and (CD3)2SO and by paramagnetic radical induced line broadening in pepiide III. In the Dxg peptides the order of solvent exposure of NH groups is Ala(1) > Ala(3) > Dxg(2), whereas in the Acnc peptides the order of solvent exposure of NH groups is Ala(1) > Acnc(2) > Ala(3). The nmr results suggest that Acnc peptides adopt folded -turn conformations with Ala(1) and Acnc(2) occupying i + 1 and i + 2 positions. In contrast, the Dxg peptides favor extended C5 conformations. The conformational differences in the two series are clearly borne out in CD studies. The solution conformations of peptides I-III are distinctly different from the -turn structure observed in crystals. Low temperature nmr spectra recorded immediately after dissolution of crystals of peptide II provide evidence for a structural transition. Introduction of an additional hydrogen-bonding function in Boc-Ala-Dpg-Ala-NHMe (VI) results in a stabilization of a consecutive -turn or incipient 310-helix in solution

Nonstandard amino acids in conformational design of peptides. Helical structures in crystals of 5-10 residue peptides containing dipropylglycine and dibutylglycine

Nonstandard amino acids dipropylglycine (Dpg) and dibutylglycine (Dbg) have been incorporated into penta- to decapeptides in order to impose local restrictions on the polypeptide chain stereochemistry. In each case, the Dpg and Dbg residues showed similar helix-forming propensity as the Aib (alpha-aminoisobutyric) residue. Further, the 310- and a-helices containing the Dbg and Dpg residues had crystal packing motifs quite similar to those found for Aib-containing peptides. Crystal structure analyses are presented for Boc-Aib-Ala-Leu-Ala-Leu-Dpg-Leu-Ala-Leu-Aib-OMe (I), space group P21 with α = 11.313(3) Å, b = 28.756(5) Å, c = 11.884 Å, β = 103.74(1)"; Boc-Leu-Dpg-Leu-Ala-Leu-Aib-OMe, polymorph a (IIa), space group P1 with a = 10.205(5) Å, b = 10.996(5) Å, c = 21.393(9) Å, α = 81.92(3)", β = 88.20(3)" γ = 89.74(3)' and polymorph b (IIb), space group P212121 with a = 9.291(1) Å, b =23.003(5) Å, c = 23.085(6): and Boc-Leu-Dbg-Val-Ala-Leu-OMe (III), space group P21 with a = 9.907(2) Å, b = 16.078(3) Å, c = 13.543(3) Å, β = 104.48(2)". The observation of helical conformations at all Dpg/Dbg residues is not entirely expected on the basis of conformational energy calculations and crystal structure observations on small homooligopeptides

Nonstandard Amino Acids in Conformational Design of Peptides. Helical Structures in Crystals of 5-10 Residue Peptides Containing Dipropylglycine and Dibutylglycine

Nonstandard amino acids dipropylglycine (Dpg) and dibutylglycine (Dbg) have been incorporated into penta- to decapeptides in order to impose local restrictions on the polypeptide chain stereochemistry. In each case, the Dpg and Dbg residues showed similar helix-forming propensity as the Aib (alpha-aminoisobutyric) residue. Further, the 310- and a-helices containing the Dbg and Dpg residues had crystal packing motifs quite similar to those found for Aib-containing peptides. Crystal structure analyses are presented for Boc-Aib-Ala-Leu-Ala-Leu-Dpg-Leu-Ala-Leu-Aib-OMe (I), space group P21 with a = 11.313(3) Å, b = 28.756(5) Å, c = 11.884 Å, beta = 103.74(1)"; Boc-Leu-Dpg-Leu-Ala-Leu-Aib-OMe, polymorph a (IIa), space group P1 with a = 10.205(5) Å, b = 10.996(5) Å, c = 21.393(9) Å, a = 81.92(3)", beta = 88.20(3)" gamma = 89.74(3)' and polymorph b (IIb), space group P212121 with a = 9.291(1) Å, b =23.003(5) Å, c = 23.085(6): and Boc-Leu-Dbg-Val-Ala-Leu-OMe (III), space group P21 with a = 9.907(2) Å, b = 16.078(3) Å, c = 13.543(3) Å, beta = 104.48(2)". The observation of helical conformations at all Dpg/Dbg residues is not entirely expected on the basis of conformational energy calculations and crystal structure observations on small homooligopeptides

Nonstandard Amino Acids in Conformational Design of Peptides. Helical Structures in Crystals of 5-10 Residue Peptides Containing Dipropylglycine and Dibutylglycine

Nonstandard amino acids dipropylglycine (Dpg) and dibutylglycine (Dbg) have been incorporated into penta- to decapeptides in order to impose local restrictions on the polypeptide chain stereochemistry. In each case, the Dpg and Dbg residues showed similar helix-forming propensity as the Aib (alpha-aminoisobutyric) residue. Further, the 310- and a-helices containing the Dbg and Dpg residues had crystal packing motifs quite similar to those found for Aib-containing peptides. Crystal structure analyses are presented for Boc-Aib-Ala-Leu-Ala-Leu-Dpg-Leu-Ala-Leu-Aib-OMe (I), space group P21 with a = 11.313(3) Å, b = 28.756(5) Å, c = 11.884 Å, beta = 103.74(1)"; Boc-Leu-Dpg-Leu-Ala-Leu-Aib-OMe, polymorph a (IIa), space group P1 with a = 10.205(5) Å, b = 10.996(5) Å, c = 21.393(9) Å, a = 81.92(3)", beta = 88.20(3)" gamma = 89.74(3)' and polymorph b (IIb), space group P212121 with a = 9.291(1) Å, b =23.003(5) Å, c = 23.085(6): and Boc-Leu-Dbg-Val-Ala-Leu-OMe (III), space group P21 with a = 9.907(2) Å, b = 16.078(3) Å, c = 13.543(3) Å, beta = 104.48(2)". The observation of helical conformations at all Dpg/Dbg residues is not entirely expected on the basis of conformational energy calculations and crystal structure observations on small homooligopeptides

Crystal structures of a nonapeptide helix containing α,α-di-n-butylglycine (Dbg), Boc-G1y-Dbg-Ala-Val-Ala-Leu-Aib-Val-Leu-OMe

Two crystal structures of a nonapeptide (anhydrous and hydrated) containing the amino acid residue &#945;, &#945;-di-n-butylglycyl, reveal a mixed 3<SUB>10</SUB>-&#945;-helical conformation. Residues 1-7 adopt &#966;, &#968; values in the helical region, with Val(8) being appreciably distorted. The Dbg residue has &#966;, &#968; values of -40, -37&#176; and -46, -407&#176; in the two crystals with the two butyl side chains mostly extended in each. Peptide molecules in the crystals pack into helical columns. The crystal parameters are: C<SUB>50</SUB> H<SUB>91</SUB> N<SUB>9</SUB> O<SUB>12</SUB>, space group P2<SUB>1</SUB>, with a= 9.789(1)&#197;;, b= 20.240(2) &#197;. c= 15.998(3) &#197;. &#946;= 103.97(1): Z= 2, R=10.3% for 1945 data observed &lt; 3&#963;(F) and C<SUB>50</SUB>H<SUB>91</SUB>N<SUB>9</SUB>O<SUB>12</SUB>&#183; 3H<SUB>2</SUB>O, space group P21 with a= 9.747(3)&#197;, b= 21.002(8) &#197;, c= 15.885(6) &#197;, &#946; = 102.22(3). Z= 2. R=13.6% for 2535 data observed &lt; 3&#963;(F) The observation of a helical conformation at Dbg suggests that the higher homologs in the &#945;, &#945;-dialkylated glycine series also have a tendency to stabilize peptide helices

Peptide Design: Crystal Structure of a Helical Peptide Module Attached to a Potentially Nonhelical Amino Terminal Segment

The pept ide Boc- Gly- Dpg- Gly- Val-A la- Leu-A ib- Val-A la- Leu- 0 Me has been designed to examine the structural consequences of placing a short segment with a low helix propensity at the amino terminus of a helical heptapeptide module. The Gl-v-Dpg-Gly segment is a potential connecting element in the synthetic construction of a helix-linker-helix motif. Crystal parameters for the peptide are P21, a = 8.651(3) Å, b = 46.826(13) Å, c = 16.245 Å, beta = 90.13(3)*, Z = 4: 2 independent molecules/asymmetric unit. The structure reveals almost identical conformations,for the two independent molecules. The backbone is completely helical for residues 2-9, with one 4 - 1 hydrogen bond and six 5 - 1 hydrogen bonds. The alpha,alpha-di-n-prop-vlglycine residue adopts a helical conjormation. Gly( I ) adopts an extended conformation resulting in a nonhelical N-terminus, with the Boc group swinging away,from the helix. The lateral association of helices in the b axis direction is unusual in that the helix axes are directed up or down (parallel or antiparallel) by pairs, etc

Peptide Design: Crystal Structure of a Helical Peptide Module Attached to a Potentially Nonhelical Amino Terminal Segment

The pept ide Boc- Gly- Dpg- Gly- Val-A la- Leu-A ib- Val-A la- Leu- 0 Me has been designed to examine the structural consequences of placing a short segment with a low helix propensity at the amino terminus of a helical heptapeptide module. The Gl-v-Dpg-Gly segment is a potential connecting element in the synthetic construction of a helix-linker-helix motif. Crystal parameters for the peptide are P21, a = 8.651(3) Å, b = 46.826(13) Å, c = 16.245 Å, beta = 90.13(3)*, Z = 4: 2 independent molecules/asymmetric unit. The structure reveals almost identical conformations,for the two independent molecules. The backbone is completely helical for residues 2-9, with one 4 - 1 hydrogen bond and six 5 - 1 hydrogen bonds. The alpha,alpha-di-n-prop-vlglycine residue adopts a helical conjormation. Gly( I ) adopts an extended conformation resulting in a nonhelical N-terminus, with the Boc group swinging away,from the helix. The lateral association of helices in the b axis direction is unusual in that the helix axes are directed up or down (parallel or antiparallel) by pairs, etc

Peptide design. Structural evaluation of potential nonhelical segments attached to helical modules

The conformations of three decapeptides containing a helical heptapeptide module attached to a potentially helix destabilizing tripeptide segment have been investigated in single crystals. X-ray diffraction studies of the sequence Boc-Gly-Dpg-Xxx-Val-Ala-Leu-Ab-Val-Ala-Leu-OMe (Xxx = Leu (l), Pro (2), and Ala (3); Dpg = alpha,alpha-di-n-propylglycine; Aib = alpha-aminoisobutyric acid) reveal helical conformations for the segment 2-9 in all three peptides. In 1 and 2 Gly(1) is not accommodated in the right-handed helix and adopts a left-handed helical conformation with positive phi, psi values. The terminal blocking group extends away from the helix in 1 and 2. In 3 the helix is continuous, encompassing residues 1-9. The Dpg residues in all three cases adopt helical conformations, even when flanked by two helix destabilizing residues as in 2. These findings suggest that the higher alpha,alpha-dialkyl residues are good helix promoters although theoretical calculations suggest the existence of a pronounced energy minimum in fully extended regions of conformational space. None of the peptides pack efficiently. The register between helices in the head-to-tail region is not good, with disordered water molecules serving as hydrogen bond bridges and as space fillers. The crystallographic parameters follow. 1: Xxx = Leu, C54H98N10O13.2H2O.C3H7OH, P212121, a = 16.399(3) &#197;, b = 18.634(3) &#197;, c = 23.241(4) &#197;. 2: Xxx = Pro, C53H94N10O13.2H2O, P212121, a = 16.468(4) &#197;, b = 18.071(4) &#197;, c = 23.397(5) &#197;. 3: Xxx = Ala, C51H92N10O13&#8727; xH2O, P21212, a = 19.289(7) &#197;, b = 35.950(12) &#197;, c = 9.570(3) &#197;