Site-Specific Glyco-Tagging of Native Proteins for the Development of Biologicals.

Glycosylation is an attractive approach to enhance biological properties of pharmaceutical proteins; however, the precise installation of glycans for structure-function studies remains challenging. Here, we describe a chemoenzymatic methodology for glyco-tagging of proteins by peptidoligase catalyzed modification of the -terminus of a protein with a synthetic glycopeptide ester having an -acetyl-glucosamine (GlcNAc) moiety to generate an -GlcNAc modified protein. The GlcNAc moiety can be elaborated into complex glycans by -glycosylation using well-defined sugar oxazolines and mutant forms of endo β--acetylglucosaminidases (ENGases).

Temporal Transitions of the Hyperinflammatory and Hypoinflammatory Phenotypes in Critical Illness.

Rationale: Systemic molecular phenotypes of critical illness are prognostically informative, yet their temporal kinetics and implications of changing phenotypes remain incompletely understood.

Objectives: To determine the temporal nature of the Hyperinflammatory and Hypoinflammatory phenotypes and assess the impact of transition between the phenotypes on mortality.

Methods: We used data from one prospective observational cohort (MARS) and two randomized controlled trials in ARDS (ALVEOLI) and sepsis (CLOVERS).

Subphenotypes in Acute Respiratory Distress Syndrome: Universal Steps Toward Treatable Traits.

Patients with acute respiratory distress syndrome (ARDS) have severe respiratory impairment requiring mechanical ventilation resulting in high mortality. Despite extensive research, no effective pharmacological interventions have been identified in unselected ARDS, which has been attributed to the considerable heterogeneity. The identification of more homogeneous subgroups through phenotyping has provided a novel method to improve our pathophysiological understanding, trial design, and, most importantly, patient care through targeted interventions.