Photolabile Linkers for Solid-Phase Synthesis

Photolabile linkers are the subjects of intense research because they allow the release of the target molecule simply by irradiation. Photochemical release of synthesis products is often facilitated without additional reagents under mild reaction conditions, which may even be environmentally friendly and appealing in the context of greener chemistry. The mild conditions also allow for applications of released material in subsequent biological screening experiments, where contamination with cleavage reagents would be detrimental. This Review pays attention to the increasing number of photolabile linkers developed for solid-phase synthesis and release and covers: (i) o-nitrobenzyloxy linkers, (ii) o-nitrobenzylamino linkers, (iii) α-substituted o-nitrobenzyl linkers, (iv) o-nitroveratryl linkers, (v) phenacyl linkers, (vi) p-alkoxyphenacyl linkers, (vii) benzoin linkers, (viii) pivaloyl linkers, and (ix) other photolabile linkers

Large genome-wide association study identifies three novel risk variants for restless legs syndrome

Funder: Scottish Government; doi: https://doi.org/10.13039/100012095Funder: Cancer Research UK (CRUK); doi: https://doi.org/10.13039/501100000289Abstract: Restless legs syndrome (RLS) is a common neurological sensorimotor disorder often described as an unpleasant sensation associated with an urge to move the legs. Here we report findings from a meta-analysis of genome-wide association studies of RLS including 480,982 Caucasians (cases = 10,257) and a follow up sample of 24,977 (cases = 6,651). We confirm 19 of the 20 previously reported RLS sequence variants at 19 loci and report three novel RLS associations; rs112716420-G (OR = 1.25, P = 1.5 × 10−18), rs10068599-T (OR = 1.09, P = 6.9 × 10−10) and rs10769894-A (OR = 0.90, P = 9.4 × 10−14). At four of the 22 RLS loci, cis-eQTL analysis indicates a causal impact on gene expression. Through polygenic risk score for RLS we extended prior epidemiological findings implicating obesity, smoking and high alcohol intake as risk factors for RLS. To improve our understanding, with the purpose of seeking better treatments, more genetics studies yielding deeper insights into the disease biology are needed

Targeted delivery of alcohol-containing payloads with antibody-drug conjugates

We herein describe the cell-specific release of alcohol-containing payloads via a sulfatase-sensitive linker in antibody-drug conjugates (ADCs). The linker shows efficient sulfatase-mediated release and high stability in human and mouse plasma. In vitro evaluation demonstrates potent antigen dependent toxicity towards breast cancer cell lines.</p

Large genome-wide association study identifies three novel risk variants for restless legs syndrome

Funder: Scottish Government; doi: https://doi.org/10.13039/100012095Funder: Cancer Research UK (CRUK); doi: https://doi.org/10.13039/501100000289Abstract: Restless legs syndrome (RLS) is a common neurological sensorimotor disorder often described as an unpleasant sensation associated with an urge to move the legs. Here we report findings from a meta-analysis of genome-wide association studies of RLS including 480,982 Caucasians (cases = 10,257) and a follow up sample of 24,977 (cases = 6,651). We confirm 19 of the 20 previously reported RLS sequence variants at 19 loci and report three novel RLS associations; rs112716420-G (OR = 1.25, P = 1.5 × 10−18), rs10068599-T (OR = 1.09, P = 6.9 × 10−10) and rs10769894-A (OR = 0.90, P = 9.4 × 10−14). At four of the 22 RLS loci, cis-eQTL analysis indicates a causal impact on gene expression. Through polygenic risk score for RLS we extended prior epidemiological findings implicating obesity, smoking and high alcohol intake as risk factors for RLS. To improve our understanding, with the purpose of seeking better treatments, more genetics studies yielding deeper insights into the disease biology are needed

Large genome-wide association study identifies three novel risk variants for restless legs syndrome

Restless legs syndrome (RLS) is a common neurological sensorimotor disorder often described as an unpleasant sensation associated with an urge to move the legs. Here we report findings from a meta-analysis of genome-wide association studies of RLS including 480,982 Caucasians (cases = 10,257) and a follow up sample of 24,977 (cases = 6,651). We confirm 19 of the 20 previously reported RLS sequence variants at 19 loci and report three novel RLS associations; rs112716420-G (OR = 1.25, P = 1.5 × 10−18), rs10068599-T (OR = 1.09, P = 6.9 × 10−10) and rs10769894-A (OR = 0.90, P = 9.4 × 10−14). At four of the 22 RLS loci, cis-eQTL analysis indicates a causal impact on gene expression. Through polygenic risk score for RLS we extended prior epidemiological findings implicating obesity, smoking and high alcohol intake as risk factors for RLS. To improve our understanding, with the purpose of seeking better treatments, more genetics studies yielding deeper insights into the disease biology are needed