Click chemistry modification of surface-bound peptides towards applications in printable electronics

This thesis shows the development of a method for the modification of surface-bound peptides. Initial attempts to functionalize amino acids with ferrocene derivatives led to a post-synthetic click grafting strategy, which could be shown to be feasible. This approach was extended to a two-step consecutive click sequence. Additionally, the grafting of Coordination clusters with the described method was investigated

High-flexibility combinatorial peptide synthesis with laser-based transfer of monomers in solid matrix material

Laser writing is used to structure surfaces in many different ways in materials and life sciences. However, combinatorial patterning applications are still limited. Here we present a method for cost-efficient combinatorial synthesis of very-high-density peptide arrays with natural and synthetic monomers. A laser automatically transfers nanometre-thin solid material spots from different donor slides to an acceptor. Each donor bears a thin polymer film, embedding one type of monomer. Coupling occurs in a separate heating step, where the matrix becomes viscous and building blocks diffuse and couple to the acceptor surface. Furthermore, we can consecutively deposit two material layers of activation reagents and amino acids. Subsequent heat-induced mixing facilitates an in situ activation and coupling of the monomers. This allows us to incorporate building blocks with click chemistry compatibility or a large variety of commercially available non-activated, for example, posttranslationally modified building blocks into the array’s peptides with >17,000 spots per cm²

Effect of Ligand Field Tuning on the SMM behavior for three related alkoxide-bridged dysprosium dimers

The synthesis and characterization of three Dy₂ compounds, [Dy₂(HL₁)₂(NO₃)₄] (<b>1</b>), [Dy₂(L₂)₂(NO₃)₄] (<b>2</b>), and [Dy₂(HL₃)₂(NO₃)₄] (<b>3</b>), formed using related tripodal ligands with a central tertiary amine bearing picolyl and alkoxy arms, 2-[(2-hydroxy-ethyl)-pyridin-2-ylmethylamino]-ethanol (H₂L₁), 2-(bis-pyridin-2-ylmethylamino)-ethanol (HL₂), and 2-(bis-pyridin-2-ylmethylamino)-propane-1,3-diol (H₂L₃), are reported. The compounds are rare examples of alkoxide-bridged {Dy₂} complexes and display capped square antiprism coordination geometry around each Dy^III ion. Changes in the ligand field environment around the Dy^III ions brought about through variations in the ligand donors can be gauged from the magnetic properties, with compounds <b>1</b> and <b>2</b> showing antiparallel coupling between the Dy^III ions and <b>3</b> showing parallel coupling. Furthermore, slow relaxation of the magnetization typical of SMM behavior could be observed for compounds <b>2</b> and <b>3</b>, suggesting that small variations in the ligand field can have a significant influence on the slow relaxation processes responsible for SMM behavior of Dy^III-based systems

The potential pathophysiological role of aldosterone and the mineralocorticoid receptor in anxiety and depression - Lessons from primary aldosteronism

High levels of aldosterone appear to be related to depressive and anxiety related behavior as demonstrated in therapy refractory depression and primary aldosteronism (PA). We analyzed data from a large register of patients with PA in order to clarify mediators and moderators of this influence. Up to 624 subjects were analyzed, however not all subjects had a complete dataset. Due to the known gender differences in subjects with PA we performed the analyses adjusted for gender. We compared subjects with (PHQ-9 ≥ 5) vs. no depressive symptomatology. 56% of men and 61% of women met this depression criterion. In women aldosterone concentration was significantly higher in depressed patients and renin levels were significantly increased with higher anxiety scores. This was not found in men. Depressive symptoms in men and women were significantly associated to BMI (men: dep vs non-dep: 29.6 vs. 28.4, p < 0.05; women: 26.9 vs. 24.5) and body weight (p < 0.05). Neither blood pressure nor electrolytes were different between depression groups. The relationship of these parameters to anxiety was less pronounced and partially unexpected: only in men higher anxiety (GAD ≥ 5) was related to lower systolic blood pressure. In conclusion, higher aldosterone appears to be associated with depressive symptoms in women, but less so in men with PA. BMI appears to be strongly and independently associated with depressive symptoms in patients with PA, independent of gender. Further studies are required to clarify the causal relationship

Differential effects of reduced mineralocorticoid receptor activation by unilateral adrenalectomy vs mineralocorticoid antagonist treatment in patients with primary aldosteronism - Implications for depression and anxiety

The mineralocorticoid receptor (MR) and its ligand aldosterone have been found to play a major role in the pathophysiology of depression. Both could be targets of therapeutic interventions. We analyzed laboratory data and questionnaires evaluating anxiety (using GAD-7 questionnaire) and depression (using PHQD questionnaire) of up to 210 patients with primary aldosteronism (PA) (82 females, 54.7 ± 12.0yrs; 128 males, 48.7 ± 12.8yrs) before and one year after initiation of specific treatment of PA by either adrenalectomy (ADX) or treatment with mineralocorticoid receptor antagonists (MRA). After ADX normalization of aldosterone excess was observed. This was associated with a significant reduction of depressive symptoms, but no significant change in GAD-7 score. MRA treatment was accompanied with persistent high aldosterone levels, but led to a significant improvement of anxiety, but no significant changes in PHQD scores. These data suggest different mechanistic pathways for depression and anxiety mediated via the MR. For treatment of depression a reduction of aldosterone levels might be relevant at CNS locations specific for aldosterone, whereas MRA targets MR more broadly, including areas, where cortisol is the main ligand. MRA may be useful in treatment of anxiety related behavior