RESUMEN
The design, synthesis and evaluation of four novel lanthanide-binding tags for paramagnetic NMR spectroscopy are reported. Each tag is based on the ((2S,2'S,2''S,2'''S)-1,1',1'',1'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetrakis(propan-2-ol)) scaffold, featuring small chiral alcohol coordinating pendants to minimise the size and hydrophobic character of each tag. The tags feature different linkers of variable length for conjugation to protein via a single cysteine residue. Each tag's ability to induce pseudocontact shifts (PCS) was assessed on a ubiquitin A28C mutant. Two enantiomeric tags of particular note, C7 and C8, produced significantly larger Δχ-tensors compared to a previously developed tag, C1, attributed to the extremely short linker utilised, limiting the mobility of the bound lanthanide ion. The C7 and C8 tags' capacity to induce PCSs was further demonstrated on GB1 Q32C and 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) S112C/C80A mutants. Whilst factors such as the choice of lanthanide ion, pH and site of conjugation influence the size of the PCSs obtained, the tags represent a significant advance in the field.
RESUMEN
An excruciating headache of instantaneous onset, or thunderclap headache, may be caused by a variety of serious disorders, including aneurysmal subarachnoid hemorrhage, cerebral venous sinus thrombosis, pituitary apoplexy, and carotid artery or vertebral artery dissection. The authors describe a patient with this type of headache who was found to have a spontaneous retroclival hematoma. A 49-year-old woman experienced an instantaneous excruciating headache. Results of computerized tomography (CT) scans of the head were normal, but on examination of the cerebrospinal fluid xanthochromia was found. Magnetic resonance (MR) imaging of the cervical spine revealed a retroclival hematoma. Three cerebral angiographic studies did not reveal the source of the hemorrhage and a repeated MR image demonstrated resolution of the hematoma. The patient made an uneventful recovery. Spontaneous retroclival hematoma is an exceedingly rare type of intracranial hemorrhage and may be associated with normal findings on CT scans. Spontaneous retroclival hematoma should be included in the differential diagnosis of thunderclap headache.