| 2. |
- Håversen, Liliana, 1963, et al.
(författare)
-
Structure-microbicidal activity relationship of synthetic fragments derived from the antibacterial alpha-helix of human lactoferrin.
- 2010
-
Ingår i: Antimicrobial agents and chemotherapy. - 1098-6596 .- 0066-4804. ; 54:1, s. 418-25
-
Tidskriftsartikel (refereegranskat)abstract
- There is a need for new microbicidal agents with therapeutic potential due to antibiotic resistance in bacteria and fungi. In this study, the structure-microbicidal activity relationship of amino acid residues 14 to 31 (sequence 14-31) from the N-terminal end, corresponding to the antibacterial alpha-helix of human lactoferrin (LF), was investigated by downsizing, alanine scanning, and substitution of amino acids. Microbicidal analysis (99% killing) was performed by a microplate assay using Escherichia coli, Staphylococcus aureus, and Candida albicans as test organisms. Starting from the N-terminal end, downsizing of peptide sequence 14-31 showed that the peptide sequence 19-31 (KCFQWQRNMRKVR, HL9) was the optimal length for antimicrobial activity. Furthermore, HL9 bound to lipid A/lipopolysaccharide, as shown by neutralizing endotoxic activity in a Limulus assay. Alanine scanning of peptide sequence 20-31 showed that Cys20, Trp23, Arg28, Lys29, or Arg31 was important for expressing full killing activity, particularly against C. albicans. Substituting the neutral hydrophilic amino acids Gln24 and Asn26 for Lys and Ala (HLopt2), respectively, enhanced microbicidal activity significantly against all test organisms compared to the amino acids natural counterpart, also, in comparison with HL9, HLopt2 had more than 10-fold-stronger fungicidal activity. Furthermore, HLopt2 was less affected by metallic salts than HL9. The microbicidal activity of HLopt2 was slightly reduced only at pH 7.0, as tested in the pH range of 4.5 to 7.5. The results showed that the microbicidal activity of synthetic peptide sequences, based on the antimicrobial alpha-helix region of LF, can be significantly enhanced by optimizing the length and substitution of neutral amino acids at specific positions, thus suggesting a sequence lead with therapeutic potential.
|
|
| 3. |
- Hesselmar, Bill, 1955, et al.
(författare)
-
Interleukin-4 receptor polymorphisms in asthma and allergy: relation to different disease phenotypes.
- 2010
-
Ingår i: Acta paediatrica. - : Wiley. - 1651-2227 .- 0803-5253. ; 99:3, s. 399-403
-
Tidskriftsartikel (refereegranskat)abstract
- Aim: Inheritance and genetic factors are supposed to influence susceptibility to asthma and allergy. We tested if single nucleotide polymorphisms (SNPs) in the IL4R gene were associated with susceptibility to such diseases, or if they were related to the phenotypic presentation of asthma and allergic rhinoconjunctivitis (ARC). Methods: Three hundred and nine 12- to 13-year-old children were included. Six SNPs in the IL4R were analysed in response to current allergic disease, and to presentation of specific asthma and ARC phenotypes. Questionnaires were used to determine allergic disease status, and skin prick tests to evaluate sensitization to common airborne allergens. Results: Less eczema was seen in individuals with the AA-genotype of rs2057768, and less ARC among those with the AA-genotype of rs2107356, especially ARC associated with sensitization to pollen. The AA-genotype of rs2057768 and the TT genotype of rs3024632 were associated with a specific asthma phenotype. Conclusion: Variations within the IL4R gene are associated with allergic diseases in children, preferably with eczema and disease phenotypes of ARC and asthma.
|
|
